Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2017, Article ID 7354260, 38 pages
https://doi.org/10.1155/2017/7354260
Review Article

Colorectal Cancer: From the Genetic Model to Posttranscriptional Regulation by Noncoding RNAs

1Departamento de Bioquímica y Biología Molecular I, Facultad de Ciencias Químicas, Universidad Complutense, 28040 Madrid, Spain
2Departamento de Oncología Radioterápica, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain

Correspondence should be addressed to Javier Turnay; se.mcu@yanrut

Received 5 December 2016; Accepted 16 February 2017; Published 10 May 2017

Academic Editor: Michael Linnebacher

Copyright © 2017 María Antonia Lizarbe et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. J. Arends, “Pathways of colorectal carcinogenesis,” Applied Immunohistochemistry and Molecular Morphology, vol. 21, no. 2, pp. 97–102, 2013. View at Publisher · View at Google Scholar · View at Scopus
  2. J. I. Barrasa, N. Olmo, M. A. Lizarbe, and J. Turnay, “Bile acids in the colon, from healthy to cytotoxic molecules,” Toxicology in Vitro, vol. 27, no. 2, pp. 964–977, 2013. View at Publisher · View at Google Scholar · View at Scopus
  3. K. Tariq and K. Ghias, “Colorectal cancer carcinogenesis: a review of mechanisms,” Cancer Biology and Medicine, vol. 13, no. 1, pp. 120–135, 2016. View at Publisher · View at Google Scholar · View at Scopus
  4. S. Tejpar and E. Van Cutsem, “Molecular and genetic defects in colorectal tumorigenesis,” Bailliere's Best Practice and Research in Clinical Gastroenterology, vol. 16, no. 2, pp. 171–185, 2002. View at Publisher · View at Google Scholar · View at Scopus
  5. D. L. Worthley, V. L. Whitehall, K. J. Spring, and B. A. Leggett, “Colorectal carcinogenesis: road maps to cancer,” World Journal of Gastroenterology, vol. 13, no. 28, pp. 3784–3791, 2007. View at Publisher · View at Google Scholar · View at Scopus
  6. E. Lages, H. Ipas, A. Guttin, H. Nesr, F. Berger, and J.-P. Issartel, “MicroRNAs: molecular features and role in cancer,” Frontiers in Bioscience, vol. 17, no. 7, pp. 2508–2540, 2011. View at Publisher · View at Google Scholar · View at Scopus
  7. G. A. Calin, C. Sevignani, C. D. Dumitru et al., “Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 9, pp. 2999–3004, 2004. View at Publisher · View at Google Scholar · View at Scopus
  8. C. M. Croce, “Causes and consequences of microRNA dysregulation in cancer,” Nature Reviews Genetics, vol. 10, no. 10, pp. 704–714, 2009. View at Publisher · View at Google Scholar · View at Scopus
  9. M. Esteller, “Non-coding RNAs in human disease,” Nature Reviews Genetics, vol. 12, no. 12, pp. 861–874, 2011. View at Publisher · View at Google Scholar · View at Scopus
  10. M. Ha and V. N. Kim, “Regulation of microRNA biogenesis,” Nature Reviews Molecular Cell Biology, vol. 15, no. 8, pp. 509–524, 2014. View at Publisher · View at Google Scholar · View at Scopus
  11. A. Hata and R. Kashima, “Dysregulation of microRNA biogenesis machinery in cancer,” Critical Reviews in Biochemistry and Molecular Biology, vol. 51, no. 3, pp. 121–134, 2016. View at Publisher · View at Google Scholar · View at Scopus
  12. J. Krol, I. Loedige, and W. Filipowicz, “The widespread regulation of microRNA biogenesis, function and decay,” Nature Reviews Genetics, vol. 11, no. 9, pp. 597–610, 2010. View at Publisher · View at Google Scholar · View at Scopus
  13. D. A. Hill, J. Ivanovich, J. R. Priest et al., “DICER1 mutations in familial pleuropulmonary blastoma,” Science, vol. 325, no. 5943, p. 965, 2009. View at Publisher · View at Google Scholar · View at Scopus
  14. S. A. Melo, S. Ropero, C. Moutinho et al., “A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function,” Nature Genetics, vol. 41, no. 3, pp. 365–370, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. A. E. Pasquinelli, “MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship,” Nature Reviews Genetics, vol. 13, no. 4, pp. 271–282, 2012. View at Publisher · View at Google Scholar · View at Scopus
  16. F. Radtke and H. Clevers, “Self-renewal and cancer of the gut: two sides of a coin,” Science, vol. 307, no. 5717, pp. 1904–1909, 2005. View at Publisher · View at Google Scholar · View at Scopus
  17. N. Barker, M. V. De Wetering, and H. Clevers, “The intestinal stem cell,” Genes and Development, vol. 22, no. 14, pp. 1856–1864, 2008. View at Publisher · View at Google Scholar · View at Scopus
  18. R. G. J. Vries, M. Huch, and H. Clevers, “Stem cells and cancer of the stomach and intestine,” Molecular Oncology, vol. 4, no. 5, pp. 373–384, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. L. A. Torre, R. L. Siegel, E. M. Ward, and A. Jemal, “Global cancer incidence and mortality rates and trends—an update,” Cancer Epidemiology Biomarkers and Prevention, vol. 25, no. 1, pp. 16–27, 2016. View at Publisher · View at Google Scholar · View at Scopus
  20. E. R. Fearon and B. Vogelstein, “A genetic model for colorectal tumorigenesis,” Cell, vol. 61, no. 5, pp. 759–767, 1990. View at Publisher · View at Google Scholar · View at Scopus
  21. A. J. Yiu and C. Y. Yiu, “Biomarkers in colorectal cancer,” Anticancer Research, vol. 36, no. 3, pp. 1093–1102, 2016. View at Google Scholar
  22. R. C. Bates and A. M. Mercurio, “The epithelial-mesenchymal transition (EMT) and colorectal cancer progression,” Cancer Biology and Therapy, vol. 4, no. 4, pp. 365–370, 2005. View at Publisher · View at Google Scholar · View at Scopus
  23. V. J. Findlay, C. Wang, D. K. Watson, and E. R. Camp, “Epithelial-to-mesenchymal transition and the cancer stem cell phenotype: insights from cancer biology with therapeutic implications for colorectal cancer,” Cancer Gene Therapy, vol. 21, no. 5, pp. 181–187, 2014. View at Publisher · View at Google Scholar · View at Scopus
  24. M. A. Puglisi, V. Tesori, W. Lattanzi, G. B. Gasbarrini, and A. Gasbarrini, “Colon cancer stem cells: controversies and perspectives,” World Journal of Gastroenterology, vol. 19, no. 20, pp. 2997–3006, 2013. View at Publisher · View at Google Scholar · View at Scopus
  25. B. M. Boman and M. S. Wicha, “Cancer stem cells: a step toward the cure,” Journal of Clinical Oncology, vol. 26, no. 17, pp. 2795–2799, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. J. A. Martínez-Climent, E. J. Andreu, and F. Prosper, “Somatic stem cells and the origin of cancer,” Clinical and Translational Oncology, vol. 8, no. 9, pp. 647–663, 2006. View at Publisher · View at Google Scholar · View at Scopus
  27. M. Baiocchi, M. Biffoni, L. Ricci-Vitiani, E. Pilozzi, and R. De Maria, “New models for cancer research: human cancer stem cell xenografts,” Current Opinion in Pharmacology, vol. 10, no. 4, pp. 380–384, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. C. A. O'Brien, A. Pollett, S. Gallinger, and J. E. Dick, “A human colon cancer cell capable of initiating tumour growth in immunodeficient mice,” Nature, vol. 445, no. 7123, pp. 106–110, 2007. View at Publisher · View at Google Scholar · View at Scopus
  29. L. Ricci-Vitiani, D. G. Lombardi, E. Pilozzi et al., “Identification and expansion of human colon-cancer-initiating cells,” Nature, vol. 445, no. 7123, pp. 111–115, 2007. View at Publisher · View at Google Scholar · View at Scopus
  30. J. Neuzil, M. Stantic, R. Zobalova et al., “Tumour-initiating cells vs. cancer 'stem' cells and CD133: what's in the name?” Biochemical and Biophysical Research Communications, vol. 355, no. 4, pp. 855–859, 2007. View at Publisher · View at Google Scholar · View at Scopus
  31. P. Dalerba, S. J. Dylla, I.-K. Park et al., “Phenotypic characterization of human colorectal cancer stem cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 24, pp. 10158–10163, 2007. View at Publisher · View at Google Scholar · View at Scopus
  32. A. P. Feinberg and B. Vogelstein, “Hypomethylation distinguishes genes of some human cancers from their normal counterparts,” Nature, vol. 301, no. 5895, pp. 89–92, 1983. View at Publisher · View at Google Scholar · View at Scopus
  33. F. J. Carmona and M. Esteller, “Epigenomics of human colon cancer,” Mutation Research—Fundamental and Molecular Mechanisms of Mutagenesis, vol. 693, no. 1-2, pp. 53–60, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. A. Goel and C. R. Boland, “Epigenetics of colorectal cancer,” Gastroenterology, vol. 143, no. 6, pp. 1442–1460.e1, 2012. View at Publisher · View at Google Scholar · View at Scopus
  35. L. Song and Y. Li, “The Role of Stem Cell DNA Methylation in Colorectal Carcinogenesis,” Stem Cell Reviews and Reports, vol. 12, no. 5, pp. 573–583, 2016. View at Publisher · View at Google Scholar · View at Scopus
  36. J. I. Barrasa, N. Olmo, A. Santiago-Gómez et al., “Histone deacetylase inhibitors upregulate MMP11 gene expression through Sp1/Smad complexes in human colon adenocarcinoma cells,” Biochimica et Biophysica Acta, vol. 1823, no. 2, pp. 570–581, 2012. View at Publisher · View at Google Scholar · View at Scopus
  37. J. Y. Fang, Y. X. Chen, J. Lu et al., “Epigenetic modification regulates both expression of tumor-associated genes and cell cycle progressing in human colon cancer cell lines: colo-320 and SW1116,” Cell Research, vol. 14, no. 3, pp. 217–226, 2004. View at Publisher · View at Google Scholar · View at Scopus
  38. A. Guzmán-Aránguez, N. Olmo, J. Turnay et al., “Differentiation of human colon adenocarcinoma cells alters the expression and intracellular localization of annexins A1, A2, and A5,” Journal of Cellular Biochemistry, vol. 94, no. 1, pp. 178–193, 2005. View at Publisher · View at Google Scholar · View at Scopus
  39. E. Lecona, J. I. Barrasa, N. Olmo, B. Llorente, J. Turnay, and M. A. Lizarbe, “Upregulation of annexin A1 expression by butyrate in human colon adenocarcinoma cells: role of p53, NF-Y, and p38 mitogen-activated protein kinase,” Molecular and Cellular Biology, vol. 28, no. 15, pp. 4665–4674, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. J. I. Barrasa, A. Santiago-Gómez, N. Olmo, M. A. Lizarbe, and J. Turnay, “Resistance to butyrate impairs bile acid-induced apoptosis in human colon adenocarcinoma cells via up-regulation of Bcl-2 and inactivation of Bax,” Biochimica et Biophysica Acta (BBA)—Molecular Cell Research, vol. 1823, no. 12, pp. 2201–2209, 2012. View at Publisher · View at Google Scholar · View at Scopus
  41. I. L. De Silanes, N. Olmo, J. Turnay et al., “Acquisition of resistance to butyrate enhances survival after stress and induces malignancy of human colon carcinoma cells,” Cancer Research, vol. 64, no. 13, pp. 4593–4600, 2004. View at Publisher · View at Google Scholar · View at Scopus
  42. N. Olmo, J. Turnay, E. Lecona et al., “Acquisition of resistance to butyrate induces resistance to luminal components and other types of stress in human colon adenocarcinoma cells,” Toxicology in Vitro, vol. 21, no. 2, pp. 254–261, 2007. View at Publisher · View at Google Scholar · View at Scopus
  43. N. Olmo, J. Turnay, P. Pérez-Ramos et al., “In vitro models for the study of the effect of butyrate on human colon adenocarcinoma cells,” Toxicology in Vitro, vol. 21, no. 2, pp. 262–270, 2007. View at Publisher · View at Google Scholar · View at Scopus
  44. P. Pérez-Ramos, N. Olmo, J. Turnay et al., “Effect of bile acids on butyrate-sensitive and -resistant human colon adenocarcinoma cells,” Nutrition and Cancer, vol. 53, no. 2, pp. 208–219, 2005. View at Publisher · View at Google Scholar · View at Scopus
  45. S. Shukla and S. M. Meeran, “Epigenetics of cancer stem cells: pathways and therapeutics,” Biochimica et Biophysica Acta, vol. 1840, no. 12, pp. 3494–3502, 2014. View at Publisher · View at Google Scholar
  46. M. Chen, J. Chen, and D. Zhang, “Exploring the secrets of long noncoding RNAs,” International Journal of Molecular Sciences, vol. 16, no. 3, pp. 5467–5496, 2015. View at Publisher · View at Google Scholar · View at Scopus
  47. J. Wang, Y.-X. Song, B. Ma et al., “Regulatory roles of non-coding RNAs in colorectal cancer,” International Journal of Molecular Sciences, vol. 16, no. 8, pp. 19886–19919, 2015. View at Publisher · View at Google Scholar · View at Scopus
  48. D. Fanale, M. Castiglia, V. Bazan, and A. Russo, “Involvement of non-coding RNAs in chemo- and radioresistance of colorectal cancer,” Advances in Experimental Medicine and Biology, vol. 937, pp. 207–228, 2016. View at Google Scholar
  49. M. Matsui and D. R. Corey, “Non-coding RNAs as drug targets,” Nature Reviews Drug Discovery, 2016. View at Publisher · View at Google Scholar · View at Scopus
  50. S. M. Berget, C. Moore, and P. A. Sharp, “Spliced segments at the 5′ terminus of adenovirus 2 late mRNA,” Proceedings of the National Academy of Sciences of the United States of America, vol. 74, no. 8, pp. 3171–3175, 1977. View at Publisher · View at Google Scholar · View at Scopus
  51. J. Liu and E. S. Maxwell, “Mouse U14 snRNA is encoded in an intron of the mouse cognate hsc70 heat shock gene,” Nucleic Acids Research, vol. 18, no. 22, pp. 6565–6571, 1990. View at Publisher · View at Google Scholar · View at Scopus
  52. E. S. Maxwell and M. J. Fournier, “The small nucleolar RNAs,” Annual Review of Biochemistry, vol. 64, pp. 897–934, 1995. View at Publisher · View at Google Scholar · View at Scopus
  53. J. E. Wilusz, H. Sunwoo, and D. L. Spector, “Long noncoding RNAs: functional surprises from the RNA world,” Genes and Development, vol. 23, no. 13, pp. 1494–1504, 2009. View at Publisher · View at Google Scholar · View at Scopus
  54. A. Fire, S. Xu, M. K. Montgomery, S. A. Kostas, S. E. Driver, and C. C. Mello, “Potent and specific genetic interference by double-stranded RNA in caenorhabditis elegans,” Nature, vol. 391, no. 6669, pp. 806–811, 1998. View at Publisher · View at Google Scholar · View at Scopus
  55. J. K. W. Lam, M. Y. T. Chow, Y. Zhang, and S. W. S. Leung, “siRNA versus miRNA as therapeutics for gene silencing,” Molecular Therapy—Nucleic Acids, vol. 4, no. 9, article no. e252, 2015. View at Publisher · View at Google Scholar · View at Scopus
  56. D. P. Bartel, “MicroRNAs: genomics, biogenesis, mechanism, and function,” Cell, vol. 116, no. 2, pp. 281–297, 2004. View at Publisher · View at Google Scholar · View at Scopus
  57. V. N. Kim, “Small RNAs: classification, biogenesis, and function,” Molecules and Cells, vol. 19, no. 1, pp. 1–15, 2005. View at Google Scholar · View at Scopus
  58. G. A. Calin, C. D. Dumitru, M. Shimizu et al., “Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 24, pp. 15524–15529, 2002. View at Publisher · View at Google Scholar · View at Scopus
  59. X. Chen, S. Fan, and E. Song, “Noncoding RNAs: new players in cancers,” in The Long and Short Non-coding RNAs in Cancer Biology, vol. 927 of Advances in Experimental Medicine and Biology, pp. 1–47, Springer, Singapore, 2016. View at Publisher · View at Google Scholar
  60. A. Kozomara and S. Griffiths-Jones, “MiRBase: annotating high confidence microRNAs using deep sequencing data,” Nucleic Acids Research, vol. 42, no. 1, pp. D68–D73, 2014. View at Publisher · View at Google Scholar · View at Scopus
  61. V. Ambros, B. Bartel, D. P. Bartel et al., “A uniform system for microRNA annotation,” RNA, vol. 9, no. 3, pp. 277–279, 2003. View at Publisher · View at Google Scholar · View at Scopus
  62. S. Griffiths-Jones, “The microRNA registry,” Nucleic Acids Research, vol. 32, pp. D109–D111, 2004. View at Publisher · View at Google Scholar · View at Scopus
  63. Z. Du, T. Sun, E. Hacisuleyman et al., “Integrative analyses reveal a long noncoding RNA-mediated sponge regulatory network in prostate cancer,” Nature Communications, vol. 7, Article ID 10982, 2016. View at Publisher · View at Google Scholar · View at Scopus
  64. N. Barron, N. Sanchez, P. Kelly, and M. Clynes, “MicroRNAs: tiny targets for engineering CHO cell phenotypes?” Biotechnology Letters, vol. 33, no. 1, pp. 11–21, 2011. View at Publisher · View at Google Scholar · View at Scopus
  65. E. F. Finnegan and A. E. Pasquinelli, “MicroRNA biogenesis: regulating the regulators,” Critical Reviews in Biochemistry and Molecular Biology, vol. 48, no. 1, pp. 51–68, 2013. View at Publisher · View at Google Scholar · View at Scopus
  66. R. B. Donker, J. F. Mouillet, T. Chu et al., “The expression profile of C19MC microRNAs in primary human trophoblast cells and exosomes,” Molecular Human Reproduction, vol. 18, no. 8, pp. 417–424, 2012. View at Publisher · View at Google Scholar · View at Scopus
  67. X. C. Ding, J. Weiler, and H. Großhans, “Regulating the regulators: mechanisms controlling the maturation of microRNAs,” Trends in Biotechnology, vol. 27, no. 1, pp. 27–36, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. M. R. Fabian and N. Sonenberg, “The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC,” Nature Structural and Molecular Biology, vol. 19, no. 6, pp. 586–593, 2012. View at Publisher · View at Google Scholar · View at Scopus
  69. A. Gurtner, E. Falcone, F. Garibaldi, and G. Piaggio, “Dysregulation of microRNA biogenesis in cancer: the impact of mutant p53 on Drosha complex activity,” Journal of Experimental and Clinical Cancer Research, vol. 35, no. 1, article no. 45, 2016. View at Publisher · View at Google Scholar · View at Scopus
  70. J. Lu, G. Getz, E. A. Miska et al., “MicroRNA expression profiles classify human cancers,” Nature, vol. 435, no. 7043, pp. 834–838, 2005. View at Publisher · View at Google Scholar · View at Scopus
  71. R.-J. Lin, Y.-C. Lin, J. Chen et al., “microRNA signature and expression of Dicer and Drosha can predict prognosis and delineate risk groups in neuroblastoma,” Cancer Research, vol. 70, no. 20, pp. 7841–7850, 2010. View at Publisher · View at Google Scholar · View at Scopus
  72. G. Martello, A. Rosato, F. Ferrari et al., “A microRNA targeting dicer for metastasis control,” Cell, vol. 141, no. 7, pp. 1195–1207, 2010. View at Publisher · View at Google Scholar · View at Scopus
  73. W. M. Merritt, Y. G. Lin, L. Y. Han et al., “Dicer, Drosha, and outcomes in patients with ovarian cancer,” New England Journal of Medicine, vol. 359, no. 25, pp. 2641–2650, 2008. View at Publisher · View at Google Scholar · View at Scopus
  74. S. Lin and R. I. Gregory, “MicroRNA biogenesis pathways in cancer,” Nature Reviews Cancer, vol. 15, no. 6, pp. 321–333, 2015. View at Publisher · View at Google Scholar · View at Scopus
  75. S. A. Melo, C. Moutinho, S. Ropero et al., “A genetic defect in exportin-5 traps precursor MicroRNAs in the nucleus of cancer cells,” Cancer Cell, vol. 18, no. 4, pp. 303–315, 2010. View at Publisher · View at Google Scholar · View at Scopus
  76. B. Kim, J.-H. Lee, J. W. Park et al., “An essential microRNA maturing microprocessor complex component DGCR8 is up-regulated in colorectal carcinomas,” Clinical and Experimental Medicine, vol. 14, no. 3, pp. 331–336, 2014. View at Publisher · View at Google Scholar · View at Scopus
  77. C. Faber, D. Horst, F. Hlubek, and T. Kirchner, “Overexpression of Dicer predicts poor survival in colorectal cancer,” European Journal of Cancer, vol. 47, no. 9, pp. 1414–1419, 2011. View at Publisher · View at Google Scholar · View at Scopus
  78. J. Stratmann, C.-J. Wang, S. Gnosa et al., “Dicer and miRNA in relation to clinicopathological variables in colorectal cancer patients,” BMC Cancer, vol. 11, article no. 345, 2011. View at Publisher · View at Google Scholar · View at Scopus
  79. D. J. Papachristou, A. Korpetinou, E. Giannopoulou et al., “Expression of the ribonucleases Drosha, Dicer, and Ago2 in colorectal carcinomas,” Virchows Archiv, vol. 459, no. 4, pp. 431–440, 2011. View at Publisher · View at Google Scholar · View at Scopus
  80. R. C. Lee, R. L. Feinbaum, and V. Ambros, “The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14,” Cell, vol. 75, no. 5, pp. 843–854, 1993. View at Publisher · View at Google Scholar · View at Scopus
  81. B. Wightman, I. Ha, and G. Ruvkun, “Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans,” Cell, vol. 75, no. 5, pp. 855–862, 1993. View at Publisher · View at Google Scholar · View at Scopus
  82. A. E. Pasquinelli, B. J. Reinhart, F. Slack et al., “Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA,” Nature, vol. 408, no. 6808, pp. 86–89, 2000. View at Publisher · View at Google Scholar · View at Scopus
  83. B. J. Reinhart, F. J. Slack, M. Basson et al., “The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans,” Nature, vol. 403, no. 6772, pp. 901–906, 2000. View at Publisher · View at Google Scholar · View at Scopus
  84. M. Lagos-Quintana, R. Rauhut, W. Lendeckel, and T. Tuschl, “Identification of novel genes coding for small expressed RNAs,” Science, vol. 294, no. 5543, pp. 853–858, 2001. View at Publisher · View at Google Scholar · View at Scopus
  85. N. C. Lau, L. P. Lim, E. G. Weinstein, and D. P. Bartel, “An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans,” Science, vol. 294, no. 5543, pp. 858–862, 2001. View at Publisher · View at Google Scholar · View at Scopus
  86. R. C. Lee and V. Ambros, “An extensive class of small RNAs in Caenorhabditis elegans,” Science, vol. 294, no. 5543, pp. 862–864, 2001. View at Publisher · View at Google Scholar · View at Scopus
  87. M. Z. Michael, S. M. O'Connor, N. G. Van Holst Pellekaan, G. P. Young, and R. J. James, “Reduced accumulation of specific MicroRNAs in colorectal neoplasia,” Molecular Cancer Research, vol. 1, no. 12, pp. 882–891, 2003. View at Google Scholar · View at Scopus
  88. J. Takamizawa, H. Konishi, K. Yanagisawa et al., “Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival,” Cancer Research, vol. 64, no. 11, pp. 3753–3756, 2004. View at Publisher · View at Google Scholar · View at Scopus
  89. A. Cimmino, G. A. Calin, M. Fabbri et al., “miR-15 and miR-16 induce apoptosis by targeting BCL2,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 39, pp. 13944–13949, 2005. View at Publisher · View at Google Scholar · View at Scopus
  90. M. V. Iorio, M. Ferracin, C.-G. Liu et al., “MicroRNA gene expression deregulation in human breast cancer,” Cancer Research, vol. 65, no. 16, pp. 7065–7070, 2005. View at Publisher · View at Google Scholar · View at Scopus
  91. S. M. Johnson, H. Grosshans, J. Shingara et al., “RAS is regulated by the let-7 microRNA family,” Cell, vol. 120, no. 5, pp. 635–647, 2005. View at Publisher · View at Google Scholar · View at Scopus
  92. K. A. O'Donnell, E. A. Wentzel, K. I. Zeller, C. V. Dang, and J. T. Mendell, “c-Myc-regulated microRNAs modulate E2F1 expression,” Nature, vol. 435, no. 7043, pp. 839–843, 2005. View at Publisher · View at Google Scholar · View at Scopus
  93. Y. Akao, Y. Nakagawa, and T. Naoe, “MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers,” Oncology Reports, vol. 16, no. 4, pp. 845–850, 2006. View at Google Scholar · View at Scopus
  94. G. T. Bommer, I. Gerin, Y. Feng et al., “p53-mediated activation of miRNA34 candidate tumor-suppressor genes,” Current Biology, vol. 17, no. 15, pp. 1298–1307, 2007. View at Publisher · View at Google Scholar · View at Scopus
  95. T.-C. Chang, E. A. Wentzel, O. A. Kent et al., “Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis,” Molecular Cell, vol. 26, no. 5, pp. 745–752, 2007. View at Publisher · View at Google Scholar · View at Scopus
  96. L. He, X. He, L. P. Lim et al., “A microRNA component of the p53 tumour suppressor network,” Nature, vol. 447, no. 7148, pp. 1130–1134, 2007. View at Publisher · View at Google Scholar · View at Scopus
  97. L. He, X. He, S. W. Lowe, and G. J. Hannon, “microRNAs join the p53 network—another piece in the tumour-suppression puzzle,” Nature Reviews Cancer, vol. 7, no. 11, pp. 819–822, 2007. View at Publisher · View at Google Scholar · View at Scopus
  98. L. He, J. M. Thomson, M. T. Hemann et al., “A microRNA polycistron as a potential human oncogene,” Nature, vol. 435, no. 7043, pp. 828–833, 2005. View at Publisher · View at Google Scholar · View at Scopus
  99. N. Raver-Shapira, E. Marciano, E. Meiri et al., “Transcriptional activation of miR-34a contributes to p53-mediated apoptosis,” Molecular Cell, vol. 26, no. 5, pp. 731–743, 2007. View at Publisher · View at Google Scholar · View at Scopus
  100. W. Tam and J. E. Dahlberg, “miR-155/BIC as an oncogenic microRNA,” Genes Chromosomes and Cancer, vol. 45, no. 2, pp. 211–212, 2006. View at Publisher · View at Google Scholar · View at Scopus
  101. V. Tarasov, P. Jung, B. Verdoodt et al., “Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest,” Cell Cycle, vol. 6, no. 13, pp. 1586–1593, 2007. View at Publisher · View at Google Scholar · View at Scopus
  102. P. M. Voorhoeve, C. le Sage, M. Schrier et al., “A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors,” Cell, vol. 124, no. 6, pp. 1169–1181, 2006. View at Publisher · View at Google Scholar · View at Scopus
  103. M. S. Ebert, J. R. Neilson, and P. A. Sharp, “MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells,” Nature Methods, vol. 4, no. 9, pp. 721–726, 2007. View at Publisher · View at Google Scholar · View at Scopus
  104. J. M. Franco-Zorrilla, A. Valli, M. Todesco et al., “Target mimicry provides a new mechanism for regulation of microRNA activity,” Nature Genetics, vol. 39, no. 8, pp. 1033–1037, 2007. View at Publisher · View at Google Scholar · View at Scopus
  105. Q. Huang, K. Gumireddy, M. Schrier et al., “The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis,” Nature Cell Biology, vol. 10, no. 2, pp. 202–210, 2008. View at Publisher · View at Google Scholar · View at Scopus
  106. L. Ma, J. Teruya-Feldstein, and R. A. Weinberg, “Tumour invasion and metastasis initiated by microRNA-10b in breast cancer,” Nature, vol. 449, no. 7163, pp. 682–688, 2007. View at Publisher · View at Google Scholar · View at Scopus
  107. M. S. Nicoloso, R. Spizzo, M. Shimizu, S. Rossi, and G. A. Calin, “MicroRNAs—the micro steering wheel of tumour metastases,” Nature Reviews Cancer, vol. 9, no. 4, pp. 293–302, 2009. View at Publisher · View at Google Scholar · View at Scopus
  108. S. F. Tavazoie, C. Alarcón, T. Oskarsson et al., “Endogenous human microRNAs that suppress breast cancer metastasis,” Nature, vol. 451, no. 7175, pp. 147–152, 2008. View at Publisher · View at Google Scholar · View at Scopus
  109. X. Chen, Y. Ba, L. Ma et al., “Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases,” Cell Research, vol. 18, no. 10, pp. 997–1006, 2008. View at Publisher · View at Google Scholar · View at Scopus
  110. S. S. C. Chim, T. K. F. Shing, E. C. W. Hung et al., “Detection and characterization of placental microRNAs in maternal plasma,” Clinical Chemistry, vol. 54, no. 3, pp. 482–490, 2008. View at Publisher · View at Google Scholar · View at Scopus
  111. C. H. Lawrie, S. Gal, H. M. Dunlop et al., “Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma,” British Journal of Haematology, vol. 141, no. 5, pp. 672–675, 2008. View at Publisher · View at Google Scholar · View at Scopus
  112. P. S. Mitchell, R. K. Parkin, E. M. Kroh et al., “Circulating microRNAs as stable blood-based markers for cancer detection,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 30, pp. 10513–10518, 2008. View at Publisher · View at Google Scholar · View at Scopus
  113. A. Bouchie, “First microRNA mimic enters clinic,” Nature Biotechnology, vol. 31, no. 7, p. 577, 2013. View at Publisher · View at Google Scholar · View at Scopus
  114. C.-W. Wu, Y.-J. Dong, Q.-Y. Liang et al., “MicroRNA-18a attenuates DNA damage repair through suppressing the expression of ataxia telangiectasia mutated in colorectal cancer,” PLoS ONE, vol. 8, no. 2, Article ID e57036, 2013. View at Publisher · View at Google Scholar · View at Scopus
  115. I. A. Asangani, S. A. K. Rasheed, D. A. Nikolova et al., “MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer,” Oncogene, vol. 27, no. 15, pp. 2128–2136, 2008. View at Publisher · View at Google Scholar · View at Scopus
  116. Y. Yang, J.-J. Yang, H. Tao, and W.-S. Jin, “MicroRNA-21 controls hTERT via PTEN in human colorectal cancer cell proliferation,” Journal of Physiology and Biochemistry, vol. 71, no. 1, pp. 59–68, 2015. View at Publisher · View at Google Scholar · View at Scopus
  117. Y. Yu, S. S. Kanwar, B. B. Patel et al., “MicroRNA-21 induces stemness by downregulating transforming growth factor beta receptor 2 (TGFβr2) in colon cancer cells,” Carcinogenesis, vol. 33, no. 1, pp. 68–76, 2012. View at Publisher · View at Google Scholar · View at Scopus
  118. W. Tang, Y. Zhu, J. Gao et al., “MicroRNA-29a promotes colorectal cancer metastasis by regulating matrix metalloproteinase 2 and E-cadherin via KLF4,” British Journal of Cancer, vol. 110, no. 2, pp. 450–458, 2014. View at Publisher · View at Google Scholar · View at Scopus
  119. T. Chen, L.-Q. Yao, Q. Shi et al., “MicroRNA-31 contributes to colorectal cancer development by targeting factor inhibiting HIF-1α (FIH-1),” Cancer Biology and Therapy, vol. 15, no. 5, pp. 516–523, 2014. View at Publisher · View at Google Scholar · View at Scopus
  120. D. Sun, F. Yu, Y. Ma et al., “MicroRNA-31 activates the RAS pathway and functions as an oncogenic MicroRNA in human colorectal cancer by repressing RAS p21 GTPase activating protein 1 (RASA1),” The Journal of Biological Chemistry, vol. 288, no. 13, pp. 9508–9518, 2013. View at Publisher · View at Google Scholar · View at Scopus
  121. R.-S. Xu, X.-D. Wu, S.-Q. Zhang et al., “The tumor suppressor gene RhoBTB1 is a novel target of miR-31 in human colon cancer,” International Journal of Oncology, vol. 42, no. 2, pp. 676–682, 2013. View at Publisher · View at Google Scholar · View at Scopus
  122. W. Wu, J. Yang, X. Feng et al., “MicroRNA-32 (miR-32) regulates phosphatase and tensin homologue (PTEN) expression and promotes growth, migration, and invasion in colorectal carcinoma cells,” Molecular Cancer, vol. 12, article 30, 2013. View at Publisher · View at Google Scholar · View at Scopus
  123. G. Zhang, H. Zhou, H. Xiao, Z. Liu, H. Tian, and T. Zhou, “MicroRNA-92a functions as an oncogene in colorectal cancer by targeting PTEN,” Digestive Diseases and Sciences, vol. 59, no. 1, pp. 98–107, 2014. View at Publisher · View at Google Scholar · View at Scopus
  124. Z. Huang, S. Huang, Q. Wang et al., “MicroRNA-95 promotes cell proliferation and targets sorting nexin 1 in human colorectal carcinoma,” Cancer Research, vol. 71, no. 7, pp. 2582–2589, 2011. View at Publisher · View at Google Scholar · View at Scopus
  125. F. Gao and W. Wang, “MicroRNA-96 promotes the proliferation of colorectal cancer cells and targets tumor protein p53 inducible nuclear protein 1, forkhead box protein O1 (FOXO1) and FOXO3a,” Molecular Medicine Reports, vol. 11, no. 2, pp. 1200–1206, 2015. View at Publisher · View at Google Scholar · View at Scopus
  126. L. Geng, B. Sun, B. Gao et al., “MicroRNA-103 promotes colorectal cancer by targeting tumor suppressor DICER and PTEN,” International Journal of Molecular Sciences, vol. 15, no. 5, pp. 8458–8472, 2014. View at Publisher · View at Google Scholar · View at Scopus
  127. R. Nagel, C. Le Sage, B. Diosdado et al., “Regulation of the adenomatous polyposis coli gene by the miR-135 family in colorectal cancer,” Cancer Research, vol. 68, no. 14, pp. 5795–5802, 2008. View at Publisher · View at Google Scholar · View at Scopus
  128. N. Valeri, P. Gasparini, M. Fabbri et al., “Modulation of mismatch repair and genomic stability by miR-155,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 15, pp. 6982–6987, 2010. View at Publisher · View at Google Scholar · View at Scopus
  129. D. Ji, Z. Chen, M. Li et al., “MicroRNA-181a promotes tumor growth and liver metastasis in colorectal cancer by targeting the tumor suppressor WIF-1,” Molecular Cancer, vol. 13, article 86, 2014. View at Publisher · View at Google Scholar · View at Scopus
  130. Z. Wei, L. Cui, Z. Mei, M. Liu, and D. Zhang, “miR-181a mediates metabolic shift in colon cancer cells via the PTEN/AKT pathway,” FEBS Letters, vol. 588, no. 9, pp. 1773–1779, 2014. View at Publisher · View at Google Scholar · View at Scopus
  131. Y. Zhang, X. Wang, Z. Wang, H. Tang, H. Fan, and Q. Guo, “miR-182 promotes cell growth and invasion by targeting forkhead box F2 transcription factor in colorectal cancer,” Oncology Reports, vol. 33, no. 5, pp. 2592–2598, 2015. View at Publisher · View at Google Scholar · View at Scopus
  132. J.-S. Mo, K. J. A. Alam, I.-H. Kang et al., “MicroRNA 196B regulates FAS-mediated apoptosis in colorectal cancer cells,” Oncotarget, vol. 6, no. 5, pp. 2843–2855, 2015. View at Publisher · View at Google Scholar · View at Scopus
  133. C. Polytarchou, D. W. Hommes, T. Palumbo et al., “MicroRNA214 is associated with progression of ulcerative colitis, and inhibition reduces development of colitis and colitis-associated cancer in mice,” Gastroenterology, vol. 149, no. 4, pp. 981–992.e11, 2015. View at Publisher · View at Google Scholar · View at Scopus
  134. D. Sun, C. Wang, S. Long et al., “C/EBP-β-activated microRNA-223 promotes tumour growth through targeting RASA1 in human colorectal cancer,” British Journal of Cancer, vol. 112, no. 9, pp. 1491–1500, 2015. View at Publisher · View at Google Scholar · View at Scopus
  135. H. Ling, K. Pickard, C. Ivan et al., “The clinical and biological significance of MIR-224 expression in colorectal cancer metastasis,” Gut, vol. 65, no. 6, pp. 977–989, 2016. View at Publisher · View at Google Scholar · View at Scopus
  136. T. Suto, T. Yokobori, R. Yajima et al., “MicroRNA-7 expression in colorectal cancer is associated with poor prognosis and regulates cetuximab sensitivity via EGFR regulation,” Carcinogenesis, vol. 36, no. 3, pp. 338–345, 2015. View at Publisher · View at Google Scholar · View at Scopus
  137. W. P. Tsang and T. T. Kwok, “The miR-18a microRNA functions as a potential tumor suppressor by targeting on K-Ras,” Carcinogenesis, vol. 30, no. 6, pp. 953–959, 2009. View at Publisher · View at Google Scholar · View at Scopus
  138. Y.-L. Ma, P. Zhang, F. Wang et al., “Human embryonic stem cells and metastatic colorectal cancer cells shared the common endogenous human microRNA-26b,” Journal of Cellular and Molecular Medicine, vol. 15, no. 9, pp. 1941–1954, 2011. View at Publisher · View at Google Scholar · View at Scopus
  139. J. Ye, X. Wu, D. Wu et al., “miRNA-27b targets vascular endothelial growth factor C to inhibit tumor progression and angiogenesis in colorectal cancer,” PLoS ONE, vol. 8, no. 4, Article ID e60687, 2013. View at Publisher · View at Google Scholar · View at Scopus
  140. M. Yamakuchi, M. Ferlito, and C. J. Lowenstein, “miR-34a repression of SIRT1 regulates apoptosis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 36, pp. 13421–13426, 2008. View at Publisher · View at Google Scholar · View at Scopus
  141. H. Peng, J. Luo, H. Hao et al., “MicroRNA-100 regulates SW620 colorectal cancer cell proliferation and invasion by targeting RAP1B,” Oncology Reports, vol. 31, no. 5, pp. 2055–2062, 2014. View at Publisher · View at Google Scholar · View at Scopus
  142. M.-B. Chen, L. Yang, P.-H. Lu et al., “MicroRNA-101 down-regulates sphingosine kinase 1 in colorectal cancer cells,” Biochemical and Biophysical Research Communications, vol. 463, no. 4, pp. 954–960, 2015. View at Publisher · View at Google Scholar · View at Scopus
  143. J. Zhang, Y. Lu, X. Yue et al., “MiR-124 suppresses growth of human colorectal cancer by inhibiting STAT3,” PLoS ONE, vol. 8, no. 8, Article ID e70300, 2013. View at Publisher · View at Google Scholar · View at Scopus
  144. V. Stiegelbauer, S. Perakis, A. Deutsch, H. Ling, A. Gerger, and M. Pichler, “MicroRNAs as novel predictive biomarkers and therapeutic targets in colorectal cancer,” World Journal of Gastroenterology, vol. 20, no. 33, pp. 11727–11735, 2014. View at Publisher · View at Google Scholar · View at Scopus
  145. Y. Liu, Y. Zhou, X. Feng et al., “MicroRNA-126 functions as a tumor suppressor in colorectal cancer cells by targeting CXCR4 via the AKT and ERK1/2 signaling pathways,” International Journal of Oncology, vol. 44, no. 1, pp. 203–210, 2014. View at Publisher · View at Google Scholar · View at Scopus
  146. Y. Zhou, X. Feng, Y.-L. Liu et al., “Down-regulation of miR-126 is associated with colorectal cancer cells proliferation, migration and invasion by targeting IRS-1 via the AKT and ERK1/2 signaling pathways,” PLoS ONE, vol. 8, no. 11, Article ID e81203, 2013. View at Publisher · View at Google Scholar · View at Scopus
  147. H. Wang, H. An, B. Wang et al., “miR-133a represses tumour growth and metastasis in colorectal cancer by targeting LIM and SH3 protein 1 and inhibiting the MAPK pathway,” European Journal of Cancer, vol. 49, no. 18, pp. 3924–3935, 2013. View at Publisher · View at Google Scholar · View at Scopus
  148. K. Zheng, W. Liu, Y. Liu, C. Jiang, and Q. Qian, “MicroRNA-133a suppresses colorectal cancer cell invasion by targeting fascin1,” Oncology Letters, vol. 9, no. 2, pp. 869–874, 2015. View at Publisher · View at Google Scholar · View at Scopus
  149. F.-T. Duan, F. Qian, K. Fang, K.-Y. Lin, W.-T. Wang, and Y.-Q. Chen, “miR-133b, a muscle-specific microRNA, is a novel prognostic marker that participates in the progression of human colorectal cancer via regulation of CXCR4 expression,” Molecular Cancer, vol. 12, article 164, 2013. View at Publisher · View at Google Scholar · View at Scopus
  150. K.-M. Xiang and X.-R. Li, “MiR-133b acts as a tumor suppressor and negatively regulates TBPL1 in colorectal cancer cells,” Asian Pacific Journal of Cancer Prevention, vol. 15, no. 8, pp. 3767–3772, 2014. View at Publisher · View at Google Scholar · View at Scopus
  151. K. Shen, Q. Liang, K. Xu et al., “MiR-139 inhibits invasion and metastasis of colorectal cancer by targeting the type I insulin-like growth factor receptor,” Biochemical Pharmacology, vol. 84, no. 3, pp. 320–330, 2012. View at Publisher · View at Google Scholar · View at Scopus
  152. L. Zhang, Y. Dong, N. Zhu et al., “microRNA-139-5p exerts tumor suppressor function by targeting NOTCH1 in colorectal cancer,” Molecular Cancer, vol. 13, article 124, 2014. View at Publisher · View at Google Scholar · View at Scopus
  153. J. Pekow, K. Meckel, U. Dougherty et al., “Tumor suppressors miR-143 and miR-145 and predicted target proteins API5, ERK5, K-RAS, and IRS-1 are differentially expressed in proximal and distal colon,” American Journal of Physiology—Gastrointestinal and Liver Physiology, vol. 308, no. 3, pp. G179–G187, 2015. View at Publisher · View at Google Scholar · View at Scopus
  154. J. Su, H. Liang, W. Yao et al., “MiR-143 and MiR-145 regulate IGF1R to suppress cell proliferation in colorectal cancer,” PLoS ONE, vol. 9, no. 12, Article ID e114420, 2014. View at Publisher · View at Google Scholar · View at Scopus
  155. T. Iwaya, T. Yokobori, N. Nishida et al., “Downregulation of miR-144 is associated with colorectal cancer progression via activation of mTOR signaling pathway,” Carcinogenesis, vol. 33, no. 12, pp. 2391–2397, 2012. View at Publisher · View at Google Scholar · View at Scopus
  156. Y. Yin, Z.-P. Yan, N.-N. Lu et al., “Downregulation of miR-145 associated with cancer progression and VEGF transcriptional activation by targeting N-RAS and IRS1,” Biochimica et Biophysica Acta (BBA)—Gene Regulatory Mechanisms, vol. 1829, no. 2, pp. 239–247, 2013. View at Publisher · View at Google Scholar · View at Scopus
  157. Y. Song, Y. Xu, Z. Wang et al., “MicroRNA-148b suppresses cell growth by targeting cholecystokinin-2 receptor in colorectal cancer,” International Journal of Cancer, vol. 131, no. 5, pp. 1042–1051, 2012. View at Publisher · View at Google Scholar · View at Scopus
  158. G. Wang, X. Cao, S. Lai et al., “Altered p53 regulation of MIR-148b and p55PIK contributes to tumor progression in colorectal cancer,” Oncogene, vol. 34, no. 7, pp. 912–921, 2015. View at Publisher · View at Google Scholar · View at Scopus
  159. B. Wang, Z.-L. Shen, Z.-D. Gao et al., “MiR-194, commonly repressed in colorectal cancer, suppresses tumor growth by regulating the MAP4K4/c-Jun/MDM2 signaling pathway,” Cell Cycle, vol. 14, no. 7, pp. 1046–1058, 2015. View at Publisher · View at Google Scholar · View at Scopus
  160. H.-J. Zhao, L.-L. Ren, Z.-H. Wang et al., “MiR-194 deregulation contributes to colorectal carcinogenesis via targeting AKT2 pathway,” Theranostics, vol. 4, no. 12, pp. 1193–1208, 2014. View at Publisher · View at Google Scholar · View at Scopus
  161. L. Liu, L. Chen, Y. Xu, R. Li, and X. Du, “microRNA-195 promotes apoptosis and suppresses tumorigenicity of human colorectal cancer cells,” Biochemical and Biophysical Research Communications, vol. 400, no. 2, pp. 236–240, 2010. View at Publisher · View at Google Scholar · View at Scopus
  162. D. J. Jin, Y. T. Fang, Z. G. Li, Z. Chen, and J. B. Xiang, “Epithelial-mesenchymal transition-associated microRNAs in colorectal cancer and drug-targeted therapies (Review),” Oncology Reports, vol. 33, no. 2, pp. 515–525, 2015. View at Publisher · View at Google Scholar · View at Scopus
  163. X.-W. Wang, X.-Q. Xi, J. Wu, Y.-Y. Wan, H.-X. Hui, and X.-F. Cao, “MicroRNA-206 attenuates tumor proliferation and migration involving the downregulation of NOTCH3 in colorectal cancer,” Oncology Reports, vol. 33, no. 3, pp. 1402–1410, 2015. View at Publisher · View at Google Scholar · View at Scopus
  164. D.-L. Chen, Z.-Q. Wang, Z.-L. Zeng et al., “Identification of microRNA-214 as a negative regulator of colorectal cancer liver metastasis by way of regulation of fibroblast growth factor receptor 1 expression,” Hepatology, vol. 60, no. 2, pp. 598–609, 2014. View at Publisher · View at Google Scholar · View at Scopus
  165. X. He, Y. Dong, C. W. Wu et al., “MicroRNA-218 inhibits cell cycle progression and promotes apoptosis in colon cancer by downregulating BMI1 polycomb ring finger oncogene,” Molecular Medicine, vol. 18, no. 12, pp. 1491–1498, 2012. View at Publisher · View at Google Scholar · View at Scopus
  166. T.-W. Ke, H.-L. Hsu, Y.-H. Wu, W. T.-L. Chen, Y.-W. Cheng, and C.-W. Cheng, “MicroRNA-224 suppresses colorectal cancer cell migration by targeting Cdc42,” Disease Markers, vol. 2014, Article ID 617150, 11 pages, 2014. View at Publisher · View at Google Scholar · View at Scopus
  167. J.-Y. Sun, Y. Huang, J.-P. Li et al., “MicroRNA-320a suppresses human colon cancer cell proliferation by directly targeting β-catenin,” Biochemical and Biophysical Research Communications, vol. 420, no. 4, pp. 787–792, 2012. View at Publisher · View at Google Scholar · View at Scopus
  168. H. Zhao, T. Dong, H. Zhou et al., “miR-320a suppresses colorectal cancer progression by targeting Rac1,” Carcinogenesis, vol. 35, no. 4, pp. 886–895, 2014. View at Publisher · View at Google Scholar · View at Scopus
  169. H. Wang, J. Wu, X. Meng et al., “Microrna-342 inhibits colorectal cancer cell proliferation and invasion by directly targeting dna methyltransferase 1,” Carcinogenesis, vol. 32, no. 7, pp. 1033–1042, 2011. View at Publisher · View at Google Scholar · View at Scopus
  170. J. Nie, L. Liu, W. Zheng et al., “microRNA-365, down-regulated in colon cancer, inhibits cell cycle progression and promotes apoptosis of colon cancer cells by probably targeting Cyclin D1 and Bcl-2,” Carcinogenesis, vol. 33, no. 1, pp. 220–225, 2012. View at Publisher · View at Google Scholar · View at Scopus
  171. Y. Wang, Q. Tang, M. Li, S. Jiang, and X. Wang, “MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA,” Biochemical and Biophysical Research Communications, vol. 444, no. 2, pp. 199–204, 2014. View at Publisher · View at Google Scholar · View at Scopus
  172. G.-J. Zhang, H. Zhou, H.-X. Xiao, Y. Li, and T. Zhou, “MiR-378 is an independent prognostic factor and inhibits cell growth and invasion in colorectal cancer,” BMC Cancer, vol. 14, article 109, 2014. View at Publisher · View at Google Scholar · View at Scopus
  173. Y. Sun, S. Shen, X. Liu et al., “MiR-429 inhibits cells growth and invasion and regulates EMT-related marker genes by targeting Onecut2 in colorectal carcinoma,” Molecular and Cellular Biochemistry, vol. 390, no. 1-2, pp. 19–30, 2014. View at Publisher · View at Google Scholar · View at Scopus
  174. J. Chai, S. Wang, D. Han, W. Dong, C. Xie, and H. Guo, “MicroRNA-455 inhibits proliferation and invasion of colorectal cancer by targeting RAF proto-oncogene serine/threonine-protein kinase,” Tumor Biology, vol. 36, no. 2, pp. 1313–1321, 2015. View at Publisher · View at Google Scholar · View at Scopus
  175. H. Nakano, T. Miyazawa, K. Kinoshita, Y. Yamada, and T. Yoshida, “Functional screening identifies a microRNA, miR-491 that induces apoptosis by targeting Bcl-X(L) in colorectal cancer cells,” International Journal of Cancer, vol. 127, no. 5, pp. 1072–1080, 2010. View at Google Scholar
  176. K. Ma, X. Pan, P. Fan et al., “Loss of miR-638 in vitro promotes cell invasion and a mesenchymal-like transition by influencing SOX2 expression in colorectal carcinoma cells,” Molecular Cancer, vol. 13, article 118, 2014. View at Publisher · View at Google Scholar · View at Scopus
  177. G. Nakajima, K. Hayashi, Y. Xi et al., “Non-coding microRNAs hsa-let-7g and hsa-miR-181b are associated with chemoresponse to S-1 in colon cancer,” Cancer Genomics and Proteomics, vol. 3, no. 5, pp. 317–324, 2006. View at Google Scholar · View at Scopus
  178. N. Nishida, S. Yamashita, K. Mimori et al., “MicroRNA-10b is a prognostic indicator in colorectal cancer and confers resistance to the chemotherapeutic agent 5-fluorouracil in colorectal cancer cells,” Annals of Surgical Oncology, vol. 19, no. 9, pp. 3065–3071, 2012. View at Publisher · View at Google Scholar · View at Scopus
  179. K. Kurokawa, T. Tanahashi, T. Iima et al., “Role of miR-19b and its target mRNAs in 5-fluorouracil resistance in colon cancer cells,” Journal of Gastroenterology, vol. 47, no. 8, pp. 883–895, 2012. View at Publisher · View at Google Scholar · View at Scopus
  180. H. Chai, M. Liu, R. Tian, X. Li, and H. Tang, “miR-20a targets BNIP2 and contributes chemotherapeutic resistance in colorectal adenocarcinoma SW480 and SW620 cell lines,” Acta Biochimica et Biophysica Sinica, vol. 43, no. 3, pp. 217–225, 2011. View at Publisher · View at Google Scholar · View at Scopus
  181. J. Shang, F. Yang, Y. Wang et al., “MicroRNA-23a antisense enhances 5-fluorouracil chemosensitivity through apaf-1/caspase-9 apoptotic pathway in colorectal cancer cells,” Journal of Cellular Biochemistry, vol. 115, no. 4, pp. 772–784, 2014. View at Publisher · View at Google Scholar · View at Scopus
  182. C.-J. Wang, J. Stratmann, Z.-G. Zhou, and X.-F. Sun, “Suppression of microRNA-31 increases sensitivity to 5-FU at an early stage, and affects cell migration and invasion in HCT-116 colon cancer cells,” BMC Cancer, vol. 10, article 616, 2010. View at Publisher · View at Google Scholar · View at Scopus
  183. B. Song, Y. Wang, Y. Xi et al., “Mechanism of chemoresistance mediated by miR-140 in human osteosarcoma and colon cancer cells,” Oncogene, vol. 28, no. 46, pp. 4065–4074, 2009. View at Publisher · View at Google Scholar · View at Scopus
  184. M. Takahashi, M. Cuatrecasas, F. Balaguer et al., “The clinical significance of MiR-148a as a predictive biomarker in patients with advanced colorectal cancer,” PLoS ONE, vol. 7, no. 10, Article ID e46684, 2012. View at Publisher · View at Google Scholar · View at Scopus
  185. B. Song, Y. Wang, M. A. Titmus et al., “Molecular mechanism of chemoresistance by miR-215 in osteosarcoma and colon cancer cells,” Molecular Cancer, vol. 9, article 96, 2010. View at Publisher · View at Google Scholar · View at Scopus
  186. V. Boni, N. Bitarte, I. Cristobal et al., “miR-192/miR-215 influence 5-fluorouracil resistance through cell cycle-mediated mechanisms complementary to its post-transcriptional thymidilate synthase regulation,” Molecular Cancer Therapeutics, vol. 9, no. 8, pp. 2265–2275, 2010. View at Publisher · View at Google Scholar · View at Scopus
  187. Y. Zhou, G. Wan, R. Spizzo et al., “miR-203 induces oxaliplatin resistance in colorectal cancer cells by negatively regulating ATM kinase,” Molecular Oncology, vol. 8, no. 1, pp. 83–92, 2014. View at Publisher · View at Google Scholar · View at Scopus
  188. K. Xu, X. Liang, K. Shen et al., “MiR-222 modulates multidrug resistance in human colorectal carcinoma by down-regulating ADAM-17,” Experimental Cell Research, vol. 318, no. 17, pp. 2168–2177, 2012. View at Publisher · View at Google Scholar · View at Scopus
  189. Y. Zhang, L. Geng, G. Talmon, and J. Wang, “MicroRNA-520g confers drug resistance by regulating p21 expression in colorectal cancer,” The Journal of Biological Chemistry, vol. 290, no. 10, pp. 6215–6225, 2015. View at Publisher · View at Google Scholar · View at Scopus
  190. M. H. Rasmussen, N. F. Jensen, L. S. Tarpgaard et al., “High expression of microRNA-625-3p is associated with poor response to first-line oxaliplatin based treatment of metastatic colorectal cancer,” Molecular Oncology, vol. 7, no. 3, pp. 637–646, 2013. View at Publisher · View at Google Scholar · View at Scopus
  191. H. Zhang, J. Tang, C. Li et al., “MiR-22 regulates 5-FU sensitivity by inhibiting autophagy and promoting apoptosis in colorectal cancer cells,” Cancer Letters, vol. 356, no. 2, pp. 781–790, 2015. View at Publisher · View at Google Scholar · View at Scopus
  192. Y. Akao, F. Khoo, M. Kumazaki, H. Shinohara, K. Miki, and N. Yamada, “Extracellular disposal of tumor-suppressor miRs-145 and -34a via microvesicles and 5-FU resistance of human colon cancer cells,” International Journal of Molecular Sciences, vol. 15, no. 1, pp. 1392–1401, 2014. View at Publisher · View at Google Scholar · View at Scopus
  193. X. Li, H. Zhao, X. Zhou, and L. Song, “Inhibition of lactate dehydrogenase A by microRNA-34a resensitizes colon cancer cells to 5-fluorouracil,” Molecular Medicine Reports, vol. 11, no. 1, pp. 577–582, 2015. View at Publisher · View at Google Scholar · View at Scopus
  194. H. Siemens, R. Jackstadt, M. Kaller, and H. Hermeking, “Repression of c-Kit by p53 is mediated by miR-34 and is associated with reduced chemoresistance, migration and stemness,” Oncotarget, vol. 4, no. 9, pp. 1399–1415, 2013. View at Publisher · View at Google Scholar · View at Scopus
  195. J. He, G. Xie, J. Tong et al., “Overexpression of microRNA-122 re-sensitizes 5-FU-resistant colon cancer cells to 5-FU through the inhibition of PKM2 in vitro and in vivo,” Cell Biochemistry and Biophysics, vol. 70, no. 2, pp. 1343–1350, 2014. View at Publisher · View at Google Scholar · View at Scopus
  196. M. Karaayvaz, H. Zhai, and J. Ju, “miR-129 promotes apoptosis and enhances chemosensitivity to 5-fluorouracil in colorectal cancer,” Cell Death and Disease, vol. 4, no. 6, article e659, 2013. View at Publisher · View at Google Scholar · View at Scopus
  197. Y. Dong, J. Zhao, C.-W. Wu et al., “Tumor suppressor functions of miR-133a in colorectal cancer,” Molecular Cancer Research, vol. 11, no. 9, pp. 1051–1060, 2013. View at Publisher · View at Google Scholar · View at Scopus
  198. H. Liu, Y. Yin, Y. Hu et al., “miR-139-5p sensitizes colorectal cancer cells to 5-fluorouracil by targeting NOTCH-1,” Pathology Research and Practice, vol. 212, no. 7, pp. 643–649, 2016. View at Publisher · View at Google Scholar · View at Scopus
  199. S. Tanaka, M. Hosokawa, T. Yonezawa, W. Hayashi, K. Ueda, and S. Iwakawa, “Induction of epithelial-mesenchymal transition and down-regulation of MIR-200c and MIR-141 in oxaliplatin-resistant colorectal cancer cells,” Biological and Pharmaceutical Bulletin, vol. 38, no. 3, pp. 435–440, 2015. View at Publisher · View at Google Scholar · View at Scopus
  200. P. M. Borralho, B. T. Kren, R. E. Castro, I. B. Moreira da Silva, C. J. Steer, and C. M. P. Rodrigues, “MicroRNA-143 reduces viability and increases sensitivity to 5-fluorouracil in HCT116 human colorectal cancer cells,” FEBS Journal, vol. 276, no. 22, pp. 6689–6700, 2009. View at Publisher · View at Google Scholar · View at Scopus
  201. X. Qian, J. Yu, Y. Yin et al., “MicroRNA-143 inhibits tumor growth and angiogenesis and sensitizes chemosensitivity to oxaliplatin in colorectal cancers,” Cell Cycle, vol. 12, no. 9, pp. 1385–1394, 2013. View at Publisher · View at Google Scholar · View at Scopus
  202. R. L. Liu, Y. Dong, Y. Z. Deng, W. J. Wang, and W. D. Li, “Tumor suppressor miR-145 reverses drug resistance by directly targeting DNA damage-related gene RAD18 in colorectal cancer,” Tumor Biology, vol. 36, no. 7, pp. 5011–5019, 2015. View at Google Scholar
  203. J. Zhang, H. Guo, H. Zhang et al., “Putative tumor suppressor miR-145 inhibits colon cancer cell growth by targeting oncogene friend leukemia virus integration 1 gene,” Cancer, vol. 117, no. 1, pp. 86–95, 2011. View at Publisher · View at Google Scholar · View at Scopus
  204. X. Liu, T. Xie, X. Mao, L. Xue, X. Chu, and L. Chen, “MicroRNA-149 increases the sensitivity of colorectal cancer cells to 5-fluorouracil by targeting forkhead box transcription factor FOXM1,” Cellular Physiology and Biochemistry, vol. 39, no. 2, pp. 617–629, 2016. View at Publisher · View at Google Scholar · View at Scopus
  205. L. Zhang, K. Pickard, V. Jenei et al., “miR-153 supports colorectal cancer progression via pleiotropic effects that enhance invasion and chemotherapeutic resistance,” Cancer Research, vol. 73, no. 21, pp. 6435–6447, 2013. View at Publisher · View at Google Scholar · View at Scopus
  206. C. C. Schimanski, K. Frerichs, F. Rahman et al., “High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells,” World Journal of Gastroenterology, vol. 15, no. 17, pp. 2089–2096, 2009. View at Publisher · View at Google Scholar · View at Scopus
  207. D. Senfter, S. Holzner, M. Kalipciyan et al., “Loss of miR-200 family in 5-fluorouracil resistant colon cancer drives lymphendothelial invasiveness in vitro,” Human Molecular Genetics, vol. 24, no. 13, pp. 3689–3698, 2015. View at Publisher · View at Google Scholar · View at Scopus
  208. T. Li, F. Gao, and X.-P. Zhang, “miR-203 enhances chemosensitivity to 5-fluorouracil by targeting thymidylate synthase in colorectal cancer,” Oncology Reports, vol. 33, no. 2, pp. 607–614, 2015. View at Publisher · View at Google Scholar · View at Scopus
  209. H. Wu, Y. Liang, L. Shen, and L. Shen, “MicroRNA-204 modulates colorectal cancer cell sensitivity in response to 5-fluorouracil-based treatment by targeting high mobility group protein A2,” Biology Open, vol. 5, no. 5, pp. 563–570, 2016. View at Publisher · View at Google Scholar · View at Scopus
  210. K. Xu, X. Liang, K. Shen et al., “miR-297 modulates multidrug resistance in human colorectal carcinoma by down-regulating MRP-2,” Biochemical Journal, vol. 446, no. 2, pp. 291–300, 2012. View at Publisher · View at Google Scholar · View at Scopus
  211. N. Bitarte, E. Bandres, V. Boni et al., “MicroRNA-451 is involved in the self-renewal, tumorigenicity, and chemoresistance of colorectal cancer stem cells,” STEM CELLS, vol. 29, no. 11, pp. 1661–1671, 2011. View at Publisher · View at Google Scholar · View at Scopus
  212. S. T. Guo, C. C. Jiang, G. P. Wang et al., “MicroRNA-497 targets insulin-like growth factor 1 receptor and has a tumour suppressive role in human colorectal cancer,” Oncogene, vol. 32, no. 15, pp. 1910–1920, 2013. View at Publisher · View at Google Scholar · View at Scopus
  213. K. K. W. To, W. W. Leung, and S. S. M. Ng, “Exploiting a novel miR-519c-HuR-ABCG2 regulatory pathway to overcome chemoresistance in colorectal cancer,” Experimental Cell Research, vol. 338, no. 2, pp. 222–231, 2015. View at Publisher · View at Google Scholar · View at Scopus
  214. K. Xu, X. Liang, D. Cui, Y. Wu, W. Shi, and J. Liu, “miR-1915 inhibits Bcl-2 to modulate multidrug resistance by increasing drug-sensitivity in human colorectal carcinoma cells,” Molecular Carcinogenesis, vol. 52, no. 1, pp. 70–78, 2013. View at Publisher · View at Google Scholar · View at Scopus
  215. M. Ragusa, A. Majorana, L. Statello et al., “Specific alterations of microRNA transcriptome and global network structure in colorectal carcinoma after cetuximab treatment,” Molecular Cancer Therapeutics, vol. 9, no. 12, pp. 3396–3409, 2010. View at Publisher · View at Google Scholar · View at Scopus
  216. J. Mlcochova, P. Faltejskova-Vychytilova, M. Ferracin et al., “MicroRNA expression profiling identifies miR-31-5p/3p as associated with time to progression in wild-type RAS metastatic colorectal cancer treated with cetuximab,” Oncotarget, vol. 6, no. 36, pp. 38695–38704, 2015. View at Publisher · View at Google Scholar · View at Scopus
  217. T. F. Hansen, A. L. Carlsen, N. H. H. Heegaard, F. B. Sørensen, and A. Jakobsen, “Changes in circulating microRNA-126 during treatment with chemotherapy and bevacizumab predicts treatment response in patients with metastatic colorectal cancer,” British Journal of Cancer, vol. 112, no. 4, pp. 624–629, 2015. View at Publisher · View at Google Scholar · View at Scopus
  218. P. Mussnich, R. Rosa, R. Bianco, A. Fusco, and D. D'Angelo, “MiR-199a-5p and miR-375 affect colon cancer cell sensitivity to cetuximab by targeting PHLPP1,” Expert Opinion on Therapeutic Targets, vol. 19, no. 8, pp. 1017–1026, 2015. View at Publisher · View at Google Scholar · View at Scopus
  219. W. Zhang, T. Winder, Y. Ning et al., “A let-7 microRNA-binding site polymorphism in 3′-untranslated region of KRAS gene predicts response in wild-type KRAS patients with metastatic colorectal cancer treated with cetuximab monotherapy,” Annals of Oncology, vol. 22, no. 1, pp. 104–109, 2011. View at Publisher · View at Google Scholar · View at Scopus
  220. A. Hata and J. Lieberman, “Dysregulation of microRNA biogenesis and gene silencing in cancer,” Science Signaling, vol. 8, no. 368, p. re3, 2015. View at Publisher · View at Google Scholar · View at Scopus
  221. C. Faber, T. Kirchner, and F. Hlubek, “The impact of microRNAs on colorectal cancer,” Virchows Archiv, vol. 454, no. 4, pp. 359–367, 2009. View at Publisher · View at Google Scholar · View at Scopus
  222. M. L. Slattery, E. Wolff, M. D. Hoffman, D. F. Pellatt, B. Milash, and R. K. Wolff, “MicroRNAs and colon and rectal cancer: differential expression by tumor location and subtype,” Genes Chromosomes and Cancer, vol. 50, no. 3, pp. 196–206, 2011. View at Publisher · View at Google Scholar · View at Scopus
  223. L. Yang, N. Belaguli, and D. H. Berger, “MicroRNA and colorectal cancer,” World Journal of Surgery, vol. 33, no. 4, pp. 638–646, 2009. View at Publisher · View at Google Scholar · View at Scopus
  224. L. Cekaite, P. W. Eide, G. E. Lind, R. I. Skotheim, and R. A. Lothe, “MicroRNAs as growth regulators, their function and biomarker status in colorectal cancer,” Oncotarget, vol. 7, no. 6, pp. 6476–6505, 2015. View at Publisher · View at Google Scholar · View at Scopus
  225. M. Liu and H. Chen, “The role of microRNAs in colorectal cancer,” Journal of Genetics and Genomics, vol. 37, no. 6, pp. 347–358, 2010. View at Publisher · View at Google Scholar · View at Scopus
  226. A. Mohammadi, B. Mansoori, and B. Baradaran, “The role of microRNAs in colorectal cancer,” Biomedicine & Pharmacotherapy, vol. 84, pp. 705–713, 2016. View at Publisher · View at Google Scholar
  227. S. Rossi, S. Kopetz, R. Davuluri, S. R. Hamilton, and G. A. Calin, “MicroRNAs, ultraconserved genes and colorectal cancers,” International Journal of Biochemistry and Cell Biology, vol. 42, no. 8, pp. 1291–1297, 2010. View at Publisher · View at Google Scholar · View at Scopus
  228. O. Slaby, M. Svoboda, J. Michalek, and R. Vyzula, “MicroRNAs in colorectal cancer: translation of molecular biology into clinical application,” Molecular Cancer, vol. 8, article 102, 2009. View at Publisher · View at Google Scholar · View at Scopus
  229. J. Thomas, M. Ohtsuka, M. Pichler, and H. Ling, “MicroRNAs: clinical relevance in colorectal cancer,” International Journal of Molecular Sciences, vol. 16, no. 12, pp. 28063–28076, 2015. View at Publisher · View at Google Scholar · View at Scopus
  230. W. K. K. Wu, P. T. Y. Law, C. W. Lee et al., “MicroRNA in colorectal cancer: from benchtop to bedside,” Carcinogenesis, vol. 32, no. 3, pp. 247–253, 2011. View at Publisher · View at Google Scholar · View at Scopus
  231. A. J. Schetter, S. Y. Leung, J. J. Sohn et al., “MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma,” The Journal of the American Medical Association, vol. 299, no. 4, pp. 425–436, 2008. View at Publisher · View at Google Scholar · View at Scopus
  232. X. Wu, X. Xu, S. Li et al., “Identification and validation of potential biomarkers for the detection of dysregulated microrna by QPCR in patients with colorectal adenocarcinoma,” PLoS ONE, vol. 10, no. 3, Article ID e0120024, 2015. View at Publisher · View at Google Scholar · View at Scopus
  233. T. Schepeler, J. T. Reinert, M. S. Ostenfeld et al., “Diagnostic and prognostic microRNAs in stage II colon cancer,” Cancer Research, vol. 68, no. 15, pp. 6416–6424, 2008. View at Publisher · View at Google Scholar · View at Scopus
  234. J. Hamfjord, A. M. Stangeland, T. Hughes et al., “Differential expression of miRNAs in colorectal cancer: comparison of paired tumor tissue and adjacent normal mucosa using high-throughput sequencing,” PLoS ONE, vol. 7, no. 4, Article ID e34150, 2012. View at Publisher · View at Google Scholar · View at Scopus
  235. J. Gu, Y. Chen, H. Huang, L. Yin, Z. Xie, and M. Q. Zhang, “Gene module based regulator inference identifying miR-139 as a tumor suppressor in colorectal cancer,” Molecular BioSystems, vol. 10, no. 12, pp. 3249–3254, 2014. View at Publisher · View at Google Scholar · View at Scopus
  236. F. L. Yong, C. W. Law, and C. W. Wang, “Potentiality of a triple microRNA classifier: MiR-193a-3p, miR-23a and miR-338-5p for early detection of colorectal cancer,” BMC Cancer, vol. 13, article no. 280, 2013. View at Publisher · View at Google Scholar · View at Scopus
  237. A. J. Schetter, H. Okayama, and C. C. Harris, “The role of MicroRNAs in colorectal cancer,” Cancer Journal, vol. 18, no. 3, pp. 244–252, 2012. View at Publisher · View at Google Scholar · View at Scopus
  238. A. Mamoori, V. Gopalan, R. A. Smith, and A. K.-Y. Lam, “Modulatory roles of microRNAs in the regulation of different signalling pathways in large bowel cancer stem cells,” Biology of the Cell, vol. 108, no. 3, pp. 51–64, 2016. View at Publisher · View at Google Scholar · View at Scopus
  239. H. Hermeking, “p53 enters the MicroRNA world,” Cancer Cell, vol. 12, no. 5, pp. 414–418, 2007. View at Publisher · View at Google Scholar · View at Scopus
  240. Y. Li, M. Lauriola, D. Kim et al., “Adenomatous polyposis coli (APC) regulates miR17-92 cluster through β-catenin pathway in colorectal cancer,” Oncogene, vol. 35, no. 35, pp. 4558–4568, 2016. View at Publisher · View at Google Scholar · View at Scopus
  241. S. Roy, Y. Yu, S. B. Padhye, F. H. Sarkar, and A. P. N. Majumdar, “Difluorinated-curcumin (CDF) restores PTEN expression in colon cancer cells by down-regulating miR-21,” PLoS ONE, vol. 8, no. 7, Article ID e68543, 2013. View at Publisher · View at Google Scholar · View at Scopus
  242. Y. Yu, P. Nangia-Makker, L. Farhana, S. G. Rajendra, E. Levi, and A. P. N. Majumdar, “miR-21 and miR-145 cooperation in regulation of colon cancer stem cells,” Molecular Cancer, vol. 14, no. 1, article 98, 2015. View at Publisher · View at Google Scholar · View at Scopus
  243. A. Moustakas and C.-H. Heldin, “The regulation of TGFβ signal transduction,” Development, vol. 136, no. 22, pp. 3699–3714, 2009. View at Publisher · View at Google Scholar · View at Scopus
  244. H. Zhang, W. Li, F. Nan et al., “MicroRNA expression profile of colon cancer stem-like cells in HT29 adenocarcinoma cell line,” Biochemical and Biophysical Research Communications, vol. 404, no. 1, pp. 273–278, 2011. View at Publisher · View at Google Scholar · View at Scopus
  245. Y. Xi, R. Shalgi, O. Fodstad, Y. Pilpel, and J. Ju, “Differentially regulated micro-RNAs and actively translated messenger RNA transcripts by tumor suppressor p53 in colon cancer,” Clinical Cancer Research, vol. 12, no. 7, part 1, pp. 2014–2024, 2006. View at Publisher · View at Google Scholar · View at Scopus
  246. V. Davalos and M. Esteller, “Unraveling the complex network of interactions between noncoding RNAs and epigenetics in cancer,” Non-Coding RNAs and Cancer, pp. 125–148, 2014. View at Publisher · View at Google Scholar · View at Scopus
  247. D. Landi, F. Gemignani, and S. Landi, “Role of variations within microRNA-binding sites in cancer,” Mutagenesis, vol. 27, no. 2, pp. 205–210, 2012. View at Publisher · View at Google Scholar · View at Scopus
  248. B. M. Ryan, A. I. Robles, and C. C. Harris, “Genetic variation in microRNA networks: the implications for cancer research,” Nature Reviews Cancer, vol. 10, no. 6, pp. 389–402, 2010. View at Publisher · View at Google Scholar · View at Scopus
  249. R. Garzon, G. Marcucci, and C. M. Croce, “Targeting microRNAs in cancer: rationale, strategies and challenges,” Nature Reviews Drug Discovery, vol. 9, no. 10, pp. 775–789, 2010. View at Publisher · View at Google Scholar · View at Scopus
  250. P. Vodicka, B. Pardini, V. Vymetalkova, and A. Naccarati, “Polymorphisms in non-coding RNA genes and their targets sites as risk factors of sporadic colorectal cancer,” in Non-Coding RNAs in Colorectal Cancer, vol. 937 of Advances in Experimental Medicine and Biology, pp. 123–149, Springer International, Cham, Switzerland, 2016. View at Publisher · View at Google Scholar
  251. X. M. Pan, X. Xiao, H. J. Qin et al., “MicroRNA variants and colorectal cancer risk: a meta-analysis,” Genetics and Molecular Research, vol. 15, no. 3, 2016. View at Publisher · View at Google Scholar
  252. L. Xu and W. Tang, “Associations of polymorphisms in mir-196a2, mir-146a and mir-149 with colorectal cancer risk: a meta-analysis,” Pathology and Oncology Research, vol. 22, no. 2, pp. 261–267, 2016. View at Publisher · View at Google Scholar · View at Scopus
  253. K. A. Zanetti, M. Haznadar, J. A. Welsh et al., “3′-UTR and functional secretor haplotypes in mannose-binding lectin 2 are associated with increased colon cancer risk in African Americans,” Cancer Research, vol. 72, no. 6, pp. 1467–1477, 2012. View at Publisher · View at Google Scholar · View at Scopus
  254. D. Landi, F. Gemignani, A. Naccarati et al., “Polymorphisms within micro-RNA-binding sites and risk of sporadic colorectal cancer,” Carcinogenesis, vol. 29, no. 3, pp. 579–584, 2008. View at Publisher · View at Google Scholar · View at Scopus
  255. B. W. Kang, H. S. Jeon, Y. S. Chae et al., “Impact of genetic variation in MicroRNA-binding site on susceptibility to colorectal cancer,” Anticancer Research, vol. 36, no. 7, pp. 3353–3361, 2016. View at Google Scholar
  256. Y. Zhao, Y. Du, S. Zhao, and Z. Guo, “Single-nucleotide polymorphisms of microRNA processing machinery genes and risk of colorectal cancer,” OncoTargets and Therapy, vol. 8, pp. 421–425, 2015. View at Publisher · View at Google Scholar · View at Scopus
  257. B. Pardini, F. Rosa, A. Naccarati et al., “Polymorphisms in microRNA genes as predictors of clinical outcomes in colorectal cancer patients,” Carcinogenesis, vol. 36, no. 1, pp. 82–86, 2015. View at Publisher · View at Google Scholar · View at Scopus
  258. J. L. Rinn, M. Kertesz, J. K. Wang et al., “Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs,” Cell, vol. 129, no. 7, pp. 1311–1323, 2007. View at Publisher · View at Google Scholar · View at Scopus
  259. R. A. Gupta, N. Shah, K. C. Wang et al., “Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis,” Nature, vol. 464, no. 7291, pp. 1071–1076, 2010. View at Publisher · View at Google Scholar · View at Scopus
  260. M. Cesana, D. Cacchiarelli, I. Legnini et al., “A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA,” Cell, vol. 147, no. 2, pp. 358–369, 2011. View at Publisher · View at Google Scholar · View at Scopus
  261. D. W. Thomson and M. E. Dinger, “Endogenous microRNA sponges: evidence and controversy,” Nature Reviews Genetics, vol. 17, no. 5, pp. 272–283, 2016. View at Publisher · View at Google Scholar · View at Scopus
  262. M. N. Rossi and F. Antonangeli, “LncRNAs: new players in apoptosis control,” International Journal of Cell Biology, vol. 2014, Article ID 473857, 7 pages, 2014. View at Publisher · View at Google Scholar · View at Scopus
  263. E. Saus, A. Brunet-Vega, S. Iraola-Guzmán, C. Pegueroles, T. Gabaldón, and C. Pericay, “Long non-coding RNAs as potential novel prognostic biomarkers in colorectal cancer,” Frontiers in Genetics, vol. 7, article no. 54, 2016. View at Publisher · View at Google Scholar · View at Scopus
  264. X. Xie, B. Tang, Y.-F. Xiao et al., “Long non-coding RNAs in colorectal cancer,” Oncotarget, vol. 7, no. 5, pp. 5226–5239, 2016. View at Publisher · View at Google Scholar · View at Scopus
  265. O. Wapinski and H. Y. Chang, “Long noncoding RNAs and human disease,” Trends in Cell Biology, vol. 21, no. 6, pp. 354–361, 2011. View at Publisher · View at Google Scholar · View at Scopus
  266. J. R. Prensner and A. M. Chinnaiyan, “The emergence of lncRNAs in cancer biology,” Cancer Discovery, vol. 1, no. 5, pp. 391–407, 2011. View at Publisher · View at Google Scholar · View at Scopus
  267. M. Ragusa, C. Barbagallo, L. Statello et al., “Non-coding landscapes of colorectal cancer,” World Journal of Gastroenterology, vol. 21, no. 41, pp. 11709–11739, 2015. View at Publisher · View at Google Scholar · View at Scopus
  268. X. Huang, T. Yuan, M. Tschannen et al., “Characterization of human plasma-derived exosomal RNAs by deep sequencing,” BMC Genomics, vol. 14, no. 1, article no. 319, 2013. View at Publisher · View at Google Scholar · View at Scopus
  269. J. Wang, X. Liu, H. Wu et al., “CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer,” Nucleic Acids Research, vol. 38, no. 16, pp. 5366–5383, 2010. View at Publisher · View at Google Scholar · View at Scopus
  270. I. J. Matouk, I. Abbasi, A. Hochberg, E. Galun, H. Dweik, and M. Akkawi, “Highly upregulated in liver cancer noncoding RNA is overexpressed in hepatic colorectal metastasis,” European Journal of Gastroenterology and Hepatology, vol. 21, no. 6, pp. 688–692, 2009. View at Publisher · View at Google Scholar · View at Scopus
  271. K. Panzitt, M. M. O. Tschernatsch, C. Guelly et al., “Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA,” Gastroenterology, vol. 132, no. 1, pp. 330–342, 2007. View at Publisher · View at Google Scholar · View at Scopus
  272. Q. Liu, J. Huang, N. Zhou et al., “LncRNA loc285194 is a p53-regulated tumor suppressor,” Nucleic Acids Research, vol. 41, no. 9, pp. 4976–4987, 2013. View at Publisher · View at Google Scholar · View at Scopus
  273. W.-C. Liang, W.-M. Fu, C.-W. Wong et al., “The LncRNA H19 promotes epithelial to mesenchymal transition by functioning as MiRNA sponges in colorectal cancer,” Oncotarget, vol. 6, no. 26, pp. 22513–22525, 2015. View at Publisher · View at Google Scholar · View at Scopus
  274. A. Keniry, D. Oxley, P. Monnier et al., “The H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and Igf1r,” Nature Cell Biology, vol. 14, no. 7, pp. 659–665, 2012. View at Publisher · View at Google Scholar · View at Scopus
  275. X. Cai and B. R. Cullen, “The imprinted H19 noncoding RNA is a primary microRNA precursor,” RNA, vol. 13, no. 3, pp. 313–316, 2007. View at Publisher · View at Google Scholar · View at Scopus
  276. W. P. Tsang, E. K. O. Ng, S. S. M. Ng et al., “Oncofetal H19-derived miR-675 regulates tumor suppressor RB in human colorectal cancer,” Carcinogenesis, vol. 31, no. 3, pp. 350–358, 2010. View at Publisher · View at Google Scholar · View at Scopus
  277. Q. Ji, L. Zhang, X. Liu et al., “Long non-coding RNA MALAT1 promotes tumour growth and metastasis in colorectal cancer through binding to SFPQ and releasing oncogene PTBP2 from SFPQ/PTBP2 complex,” British Journal of Cancer, vol. 111, no. 4, pp. 736–748, 2014. View at Publisher · View at Google Scholar · View at Scopus
  278. L. D. Graham, S. K. Pedersen, G. S. Brown et al., “Colorectal Neoplasia Differentially Expressed (CRNDE), a Novel Gene with Elevated Expression in Colorectal Adenomas and Adenocarcinomas,” Genes and Cancer, vol. 2, no. 8, pp. 829–840, 2011. View at Publisher · View at Google Scholar · View at Scopus
  279. M. Svoboda, J. Slyskova, M. Schneiderova et al., “HOTAIR long non-coding RNA is a negative prognostic factor not only in primary tumors, but also in the blood of colorectal cancer patients,” Carcinogenesis, vol. 35, no. 7, pp. 1510–1515, 2014. View at Publisher · View at Google Scholar · View at Scopus
  280. B. C. Ellis, P. L. Molloy, and L. D. Graham, “CRNDE: a long non-coding RNA involved in CanceR Neurobiology, and DEvelopment,” Frontiers in Genetics, vol. 3, article 270, 2012. View at Publisher · View at Google Scholar · View at Scopus
  281. M. Hajjari and A. Salavaty, “HOTAIR: an oncogenic long non-coding RNA in different cancers,” Cancer Biology and Medicine, vol. 12, no. 1, pp. 1–9, 2015. View at Publisher · View at Google Scholar · View at Scopus
  282. X. Ge, Y. Chen, X. Liao et al., “Overexpression of long noncoding RNA PCAT-1 is a novel biomarker of poor prognosis in patients with colorectal cancer,” Medical Oncology, vol. 30, no. 2, article 588, 2013. View at Publisher · View at Google Scholar · View at Scopus
  283. X. He, X. Tan, X. Wang et al., “C-Myc-activated long noncoding RNA CCAT1 promotes colon cancer cell proliferation and invasion,” Tumor Biology, vol. 35, no. 12, pp. 12181–12188, 2014. View at Publisher · View at Google Scholar · View at Scopus
  284. H. Lee, C. Kim, J.-L. Ku et al., “A long non-coding RNA snaR contributes to 5-fluorouracil resistance in human colon cancer cells,” Molecules and Cells, vol. 37, no. 7, pp. 540–546, 2014. View at Publisher · View at Google Scholar · View at Scopus
  285. Z. Bian, L. Jin, J. Zhang et al., “LncRNA—UCA1 enhances cell proliferation and 5-fluorouracil resistance in colorectal cancer by inhibiting miR-204-5p,” Scientific Reports, vol. 6, article 23892, 2016. View at Publisher · View at Google Scholar · View at Scopus
  286. A. Diaz-Lagares, A. B. Crujeiras, P. Lopez-Serra et al., “Epigenetic inactivation of the p53-induced long noncoding RNA TP53 target 1 in human cancer,” Proceedings of the National Academy of Sciences, vol. 113, no. 47, pp. E7535–E7544, 2016. View at Publisher · View at Google Scholar
  287. G. Wang, Z. Li, Q. Zhao et al., “LincRNA-p21 enhances the sensitivity of radiotherapy for human colorectal cancer by targeting the Wnt/β-catenin signaling pathway,” Oncology Reports, vol. 31, no. 4, pp. 1839–1845, 2014. View at Publisher · View at Google Scholar · View at Scopus
  288. N. Dimitrova, J. R. Zamudio, R. M. Jong et al., “LincRNA-p21 activates p21 in cis to promote polycomb target gene expression and to enforce the G1/S checkpoint,” Molecular Cell, vol. 54, no. 5, pp. 777–790, 2014. View at Publisher · View at Google Scholar · View at Scopus
  289. M.-T. Hsu and M. Coca-Prados, “Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells,” Nature, vol. 280, no. 5720, pp. 339–340, 1979. View at Publisher · View at Google Scholar · View at Scopus
  290. J. M. Nigro, K. R. Cho, E. R. Fearon et al., “Scrambled exons,” Cell, vol. 64, no. 3, pp. 607–613, 1991. View at Publisher · View at Google Scholar · View at Scopus
  291. J. Li, J. Yang, P. Zhou et al., “Circular RNAs in cancer: novel insights into origins, properties, functions and implications,” American Journal of Cancer Research, vol. 5, no. 2, pp. 472–480, 2015. View at Google Scholar
  292. Y. Zhang, X.-O. Zhang, T. Chen et al., “Circular intronic long noncoding RNAs,” Molecular Cell, vol. 51, no. 6, pp. 792–806, 2013. View at Publisher · View at Google Scholar · View at Scopus
  293. A. Bachmayr-Heyda, A. T. Reiner, K. Auer et al., “Correlation of circular RNA abundance with proliferation—exemplified with colorectal and ovarian cancer, idiopathic lung fibrosis, and normal human tissues,” Scientific Reports, vol. 5, article 8057, 2015. View at Publisher · View at Google Scholar · View at Scopus
  294. Y. Li, Q. Zheng, C. Bao et al., “Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis,” Cell Research, vol. 25, no. 8, pp. 981–984, 2015. View at Publisher · View at Google Scholar · View at Scopus
  295. F. Wang, A. J. Nazarali, and S. Ji, “Circular RNAs as potential biomarkers for cancer diagnosis and therapy,” American Journal of Cancer Research, vol. 6, no. 6, pp. 1167–1176, 2016. View at Google Scholar
  296. S. Memczak, M. Jens, A. Elefsinioti et al., “Circular RNAs are a large class of animal RNAs with regulatory potency,” Nature, vol. 495, no. 7441, pp. 333–338, 2013. View at Publisher · View at Google Scholar · View at Scopus
  297. T. B. Hansen, T. I. Jensen, B. H. Clausen et al., “Natural RNA circles function as efficient microRNA sponges,” Nature, vol. 495, no. 7441, pp. 384–388, 2013. View at Publisher · View at Google Scholar · View at Scopus
  298. N. Zhang, X. Li, C. W. Wu et al., “MicroRNA-7 is a novel inhibitor of YY1 contributing to colorectal tumorigenesis,” Oncogene, vol. 32, no. 42, pp. 5078–5088, 2013. View at Publisher · View at Google Scholar · View at Scopus
  299. L. Peng, X. Q. Yuan, and G. C. Li, “The emerging landscape of circular RNA ciRS-7 in cancer (Review),” Oncology Reports, vol. 33, no. 6, pp. 2669–2674, 2015. View at Publisher · View at Google Scholar · View at Scopus
  300. W. R. Jeck and N. E. Sharpless, “Detecting and characterizing circular RNAs,” Nature Biotechnology, vol. 32, no. 5, pp. 453–461, 2014. View at Publisher · View at Google Scholar · View at Scopus
  301. J. Guarnerio, M. Bezzi, J. C. Jeong et al., “Oncogenic role of fusion-circRNAs derived from cancer-associated chromosomal translocations,” Cell, vol. 165, no. 2, pp. 289–302, 2016. View at Google Scholar
  302. P. Piedbois, P. Rougier, M. Buyse et al., “Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer,” Journal of Clinical Oncology, vol. 16, no. 1, pp. 301–308, 1998. View at Google Scholar
  303. B. Gustavsson, G. Carlsson, D. MacHover et al., “A review of the evolution of systemic chemotherapy in the management of colorectal cancer,” Clinical Colorectal Cancer, vol. 14, no. 1, pp. 1–10, 2015. View at Publisher · View at Google Scholar · View at Scopus
  304. V. Heinemann, L. F. von Weikersthal, T. Decker et al., “FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial,” The Lancet Oncology, vol. 15, no. 10, pp. 1065–1075, 2014. View at Publisher · View at Google Scholar · View at Scopus
  305. F. F. Kabbinavar, J. Hambleton, R. D. Mass, H. I. Hurwitz, E. Bergsland, and S. Sarkar, “Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer,” Journal of Clinical Oncology, vol. 23, no. 16, pp. 3706–3712, 2005. View at Publisher · View at Google Scholar · View at Scopus
  306. S.-Y. Lee and S. C. Oh, “Advances of targeted therapy in treatment of unresectable metastatic colorectal cancer,” BioMed Research International, vol. 2016, Article ID 7590245, 14 pages, 2016. View at Publisher · View at Google Scholar · View at Scopus
  307. E. Van Cutsem, C.-H. Köhne, I. Láng et al., “Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status,” Journal of Clinical Oncology, vol. 29, no. 15, pp. 2011–2019, 2011. View at Publisher · View at Google Scholar · View at Scopus
  308. F. Ciardiello and G. Tortora, “EGFR antagonists in cancer treatment,” New England Journal of Medicine, vol. 358, no. 11, pp. 1096–1174, 2008. View at Publisher · View at Google Scholar · View at Scopus
  309. D. Rodrigues, A. Longatto-Filho, and S. F. Martins, “Predictive biomarkers in colorectal cancer: from the single therapeutic target to a plethora of options,” BioMed Research International, vol. 2016, Article ID 6896024, 12 pages, 2016. View at Publisher · View at Google Scholar
  310. R. G. Amado, M. Wolf, M. Peeters et al., “Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer,” Journal of Clinical Oncology, vol. 26, no. 10, pp. 1626–1634, 2008. View at Publisher · View at Google Scholar · View at Scopus
  311. C. Bokemeyer, I. Bondarenko, A. Makhson et al., “Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer,” Journal of Clinical Oncology, vol. 27, no. 5, pp. 663–671, 2009. View at Publisher · View at Google Scholar · View at Scopus
  312. C. S. Karapetis, S. Khambata-Ford, D. J. Jonker et al., “K-ras mutations and benefit from cetuximab in advanced colorectal cancer,” The New England Journal of Medicine, vol. 359, no. 17, pp. 1757–1765, 2008. View at Publisher · View at Google Scholar · View at Scopus
  313. J.-Y. Douillard, K. S. Oliner, S. Siena et al., “Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer,” The New England Journal of Medicine, vol. 369, no. 11, pp. 1023–1034, 2013. View at Publisher · View at Google Scholar · View at Scopus
  314. T. S. Maughan, R. A. Adams, C. G. Smith et al., “Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial,” The Lancet, vol. 377, no. 9783, pp. 2103–2114, 2011. View at Publisher · View at Google Scholar · View at Scopus
  315. M. V. Blagosklonny, “How Avastin potentiates chemotherapeutic drugs: action and reaction in antiangiogenic therapy,” Cancer Biology and Therapy, vol. 4, no. 12, pp. 1307–1310, 2005. View at Publisher · View at Google Scholar · View at Scopus
  316. M. A. Bruhn, A. R. Townsend, C. Khoon Lee et al., “Proangiogenic tumor proteins as potential predictive or prognostic biomarkers for bevacizumab therapy in metastatic colorectal cancer,” International Journal of Cancer, vol. 135, no. 3, pp. 731–741, 2014. View at Publisher · View at Google Scholar · View at Scopus
  317. H. Hayashi, T. Arao, K. Matsumoto et al., “Biomarkers of reactive resistance and early disease progression during chemotherapy plus bevacizumab treatment for colorectal carcinoma,” Oncotarget, vol. 5, no. 9, pp. 2588–2595, 2014. View at Publisher · View at Google Scholar · View at Scopus
  318. F. Loupakis, C. Cremolini, A. Fioravanti et al., “Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line FOLFOXIRI plus bevacizumab schedule in metastatic colorectal cancer,” British Journal of Cancer, vol. 104, no. 8, pp. 1262–1269, 2011. View at Publisher · View at Google Scholar · View at Scopus
  319. M. Scartozzi, L. Vincent, M. Chiron, and S. Cascinu, “Aflibercept, a new way to target angiogenesis in the second line treatment of metastatic colorectal cancer (mCRC),” Targeted Oncology, vol. 11, no. 4, pp. 489–500, 2016. View at Publisher · View at Google Scholar · View at Scopus
  320. R. Obermannová, E. Van Cutsem, T. Yoshino et al., “Subgroup analysis in RAISE: a randomized, double-blind phase III study of irinotecan, folinic acid, and 5-fluorouracil (FOLFIRI) plus ramucirumab or placebo in patients with metastatic colorectal carcinoma progression,” Annals of Oncology, vol. 27, no. 11, pp. 2082–2090, 2016. View at Google Scholar
  321. Y. Ohhara, N. Fukuda, S. Takeuchi et al., “Role of targeted therapy in metastatic colorectal cancer,” World Journal of Gastrointestinal Oncology, vol. 8, no. 9, pp. 642–655, 2016. View at Publisher · View at Google Scholar
  322. A. Sanchez-Gastaldo, R. Gonzalez-Exposito, and R. Garcia-Carbonero, “Ramucirumab clinical development: an emerging role in gastrointestinal tumors,” Targeted Oncology, vol. 11, no. 4, pp. 479–487, 2016. View at Publisher · View at Google Scholar · View at Scopus
  323. S. M. Wilhelm, J. Dumas, L. Adnane et al., “Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity,” International Journal of Cancer, vol. 129, no. 1, pp. 245–255, 2011. View at Publisher · View at Google Scholar · View at Scopus
  324. J. Li, S. Qin, R. Xu et al., “Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial,” The Lancet Oncology, vol. 16, no. 6, pp. 619–629, 2015. View at Publisher · View at Google Scholar · View at Scopus
  325. C. Lo Nigro, V. Ricci, D. Vivenza et al., “Prognostic and predictive biomarkers in metastatic colorectal cancer anti-EGFR therapy,” World Journal of Gastroenterology, vol. 22, no. 30, pp. 6944–6954, 2016. View at Publisher · View at Google Scholar · View at Scopus
  326. J.-S. Kim, C. Lee, C. L. Bonifant, H. Ressom, and T. Waldman, “Activation of p53-dependent growth suppression in human cells by mutations in PTEN or PIK3CA,” Molecular and Cellular Biology, vol. 27, no. 2, pp. 662–677, 2007. View at Publisher · View at Google Scholar · View at Scopus
  327. A. Sartore-Bianchi, M. Martini, F. Molinari et al., “PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies,” Cancer Research, vol. 69, no. 5, pp. 1851–1857, 2009. View at Publisher · View at Google Scholar · View at Scopus
  328. K. Lee and L. R. Ferguson, “MicroRNA biomarkers predicting risk, initiation and progression of colorectal cancer,” World Journal of Gastroenterology, vol. 22, no. 33, pp. 7389–7401, 2016. View at Publisher · View at Google Scholar
  329. Z. Li and T. M. Rana, “Therapeutic targeting of microRNAs: current status and future challenges,” Nature Reviews Drug Discovery, vol. 13, no. 8, pp. 622–638, 2014. View at Publisher · View at Google Scholar · View at Scopus
  330. R. Yi, Y. Li, F. L. Wang, G. Miao, R. M. Qi, and Y. Y. Zhao, “MicroRNAs as diagnostic and prognostic biomarkers in colorectal cancer,” World Journal of Gastrointestinal Oncology, vol. 8, no. 4, pp. 330–340, 2016. View at Google Scholar
  331. X. Li, J. Nie, Q. Mei, and W.-D. Han, “MicroRNAs: novel immunotherapeutic targets in colorectal carcinoma,” World Journal of Gastroenterology, vol. 22, no. 23, pp. 5317–5331, 2016. View at Publisher · View at Google Scholar · View at Scopus
  332. M. K. Boisen, C. Dehlendorff, D. Linnemann et al., “MicroRNA expression in formalin-fixed paraffin-embedded cancer tissue: identifying reference MicroRNAs and variability,” BMC Cancer, vol. 15, article 1024, 2015. View at Publisher · View at Google Scholar · View at Scopus
  333. Y. Xuan, H. Yang, L. Zhao et al., “MicroRNAs in colorectal cancer: small molecules with big functions,” Cancer Letters, vol. 360, no. 2, pp. 89–105, 2015. View at Publisher · View at Google Scholar · View at Scopus
  334. T. El-Hefnawy, S. Raja, L. Kelly et al., “Characterization of amplifiable, circulating RNA in plasma and its potential as a tool for cancer diagnostics,” Clinical Chemistry, vol. 50, no. 3, pp. 564–573, 2004. View at Publisher · View at Google Scholar · View at Scopus
  335. E. E. Creemers, A. J. Tijsen, and Y. M. Pinto, “Circulating MicroRNAs: novel biomarkers and extracellular communicators in cardiovascular disease?” Circulation Research, vol. 110, no. 3, pp. 483–495, 2012. View at Publisher · View at Google Scholar · View at Scopus
  336. L. Pigati, S. C. S. Yaddanapudi, R. Iyengar et al., “Selective release of MicroRNA species from normal and malignant mammary epithelial cells,” PLoS ONE, vol. 5, no. 10, Article ID e13515, 2010. View at Publisher · View at Google Scholar · View at Scopus
  337. T. S. Chen, R. C. Lai, M. M. Lee, A. B. H. Choo, C. N. Lee, and S. K. Lim, “Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs,” Nucleic Acids Research, vol. 38, no. 1, pp. 215–224, 2010. View at Publisher · View at Google Scholar · View at Scopus
  338. S. Kubota, M. Chiba, M. Watanabe, M. Sakamoto, and N. Watanabe, “Secretion of small/microRNAs including miR-638 into extracellular spaces by sphingomyelin phosphodiesterase 3,” Oncology Reports, vol. 33, no. 1, pp. 67–73, 2015. View at Publisher · View at Google Scholar · View at Scopus
  339. G.-H. Liu, Z.-G. Zhou, R. Chen et al., “Serum miR-21 and miR-92a as biomarkers in the diagnosis and prognosis of colorectal cancer,” Tumor Biology, vol. 34, no. 4, pp. 2175–2181, 2013. View at Publisher · View at Google Scholar · View at Scopus
  340. C. W. Wu, S. S. M. Ng, Y. J. Dong et al., “Detection of miR-92a and miR-21 in stool samples as potential screening biomarkers for colorectal cancer and polyps,” Gut, vol. 61, no. 5, pp. 739–745, 2012. View at Publisher · View at Google Scholar · View at Scopus
  341. Z. Kanaan, S. N. Rai, M. R. Eichenberger et al., “Plasma MiR-21: a potential diagnostic marker of colorectal cancer,” Annals of Surgery, vol. 256, no. 3, pp. 544–551, 2012. View at Publisher · View at Google Scholar · View at Scopus
  342. S. T. Aherne, S. F. Madden, D. J. Hughes et al., “Circulating miRNAs miR-34a and miR-150 associated with colorectal cancer progression,” BMC Cancer, vol. 15, article 329, 2015. View at Publisher · View at Google Scholar · View at Scopus
  343. H. Imaoka, Y. Toiyama, H. Fujikawa et al., “Circulating microRNA-1290 as a novel diagnostic and prognostic biomarker in human colorectal cancer,” Annals of Oncology, vol. 27, no. 10, pp. 1879–1886, 2016. View at Publisher · View at Google Scholar
  344. Z. Kanaan, H. Roberts, M. R. Eichenberger et al., “A plasma MicroRNA panel for detection of colorectal adenomas: a step toward more precise screening for colorectal cancer,” Annals of Surgery, vol. 258, no. 3, pp. 400–408, 2013. View at Publisher · View at Google Scholar · View at Scopus
  345. C. W. Wu, S. C. Ng, Y. Dong et al., “Identification of microrna-135b in stool as a potential noninvasive biomarker for colorectal cancer and adenoma,” Clinical Cancer Research, vol. 20, no. 11, pp. 2994–3002, 2014. View at Publisher · View at Google Scholar · View at Scopus
  346. Y. Koga, N. Yamazaki, Y. Yamamoto et al., “Fecal miR-106a is a useful marker for colorectal cancer patients with false-negative results in immunochemical fecal occult blood test,” Cancer Epidemiology Biomarkers and Prevention, vol. 22, no. 10, pp. 1844–1852, 2013. View at Publisher · View at Google Scholar · View at Scopus
  347. F. E. Ahmed, “miRNA as markers for the diagnostic screening of colon cancer,” Expert Review of Anticancer Therapy, vol. 14, no. 4, pp. 463–485, 2014. View at Publisher · View at Google Scholar · View at Scopus
  348. F. Simmer, S. Venderbosch, J. R. Dijkstra et al., “MicroRNA-143 is a putative predictive factor for the response to fluoropyrimidine-based chemotherapy in patients with metastatic colorectal cancer,” Oncotarget, vol. 6, no. 26, pp. 22996–23007, 2015. View at Publisher · View at Google Scholar · View at Scopus
  349. L. Pérez-Carbonell, F. A. Sinicrope, S. R. Alberts et al., “MiR-320e is a novel prognostic biomarker in colorectal cancer,” British Journal of Cancer, vol. 113, no. 1, pp. 83–90, 2015. View at Publisher · View at Google Scholar · View at Scopus
  350. H.-C. Lee, J. G. Kim, Y. S. Chae et al., “Prognostic impact of microRNA-related gene polymorphisms on survival of patients with colorectal cancer,” Journal of Cancer Research and Clinical Oncology, vol. 136, no. 7, pp. 1073–1078, 2010. View at Publisher · View at Google Scholar · View at Scopus
  351. F. Graziano, E. Canestrari, F. Loupakis et al., “Genetic modulation of the Let-7 microRNA binding to KRAS 3′-untranslated region and survival of metastatic colorectal cancer patients treated with salvage cetuximab-irinotecan,” Pharmacogenomics Journal, vol. 10, no. 5, pp. 458–464, 2010. View at Publisher · View at Google Scholar · View at Scopus
  352. T. F. Hansen, R. D. P. Christensen, R. F. Andersen, F. B. Sørensen, A. Johnsson, and A. Jakobsen, “MicroRNA-126 and epidermal growth factor-like domain 7-an angiogenic couple of importance in metastatic colorectal cancer. Results from the Nordic ACT trial,” British Journal of Cancer, vol. 109, no. 5, pp. 1243–1251, 2013. View at Publisher · View at Google Scholar · View at Scopus
  353. W. Ma, J. Yu, X. Qi et al., “Radiation-induced microRNA-622 causes radioresistance in colorectal cancer cells by down-regulating Rb,” Oncotarget, vol. 6, no. 18, pp. 15984–15994, 2015. View at Publisher · View at Google Scholar · View at Scopus
  354. Y. Zhang, J. Yu, H. Liu et al., “Novel epigenetic CREB-miR-630 signaling axis regulates radiosensitivity in colorectal cancer,” PLoS ONE, vol. 10, no. 8, Article ID e0133870, 2015. View at Publisher · View at Google Scholar · View at Scopus
  355. L. Zheng, Y. Zhang, Y. Liu et al., “MiR-106b induces cell radioresistance via the PTEN/PI3K/AKT pathways and p21 in colorectal cancer,” Journal of Translational Medicine, vol. 13, article 252, 2015. View at Publisher · View at Google Scholar · View at Scopus
  356. A. F. Christopher, R. P. Kaur, G. Kaur, A. Kaur, V. Gupta, and P. Bansal, “MicroRNA therapeutics: discovering novel targets and developing specific therapy,” Perspectives in Clinical Research, vol. 7, no. 2, pp. 68–74, 2016. View at Publisher · View at Google Scholar
  357. J. Jung, C. Yeom, Y.-S. Choi et al., “Simultaneous inhibition of multiple oncogenic miRNAs by a multi-potent microRNA sponge,” Oncotarget, vol. 6, no. 24, pp. 20370–20387, 2015. View at Publisher · View at Google Scholar · View at Scopus
  358. M. S. Ebert and P. A. Sharp, “MicroRNA sponges: progress and possibilities,” RNA, vol. 16, no. 11, pp. 2043–2050, 2010. View at Publisher · View at Google Scholar · View at Scopus
  359. F. R. Kulcheski, A. P. Christoff, and R. Margis, “Circular RNAs are miRNA sponges and can be used as a new class of biomarker,” Journal of Biotechnology, vol. 238, pp. 42–51, 2016. View at Publisher · View at Google Scholar
  360. W.-Y. Choi, A. J. Giraldez, and A. F. Schier, “Target protectors reveal dampening and balancing of nodal agonist and antagonist by miR-430,” Science, vol. 318, no. 5848, pp. 271–274, 2007. View at Publisher · View at Google Scholar · View at Scopus
  361. K. Gumireddy, D. D. Young, X. Xiong, J. B. Hogenesch, Q. Huang, and A. Deiters, “Small-molecule inhibitors of microRNA miR-21 function,” Angewandte Chemie—International Edition, vol. 47, no. 39, pp. 7482–7484, 2008. View at Publisher · View at Google Scholar · View at Scopus
  362. V. T. Tripp and D. D. Young, “Discovery of small molecule modifiers of microRNAs for the treatment of HCV infection,” Methods in Molecular Biology, vol. 1103, pp. 153–163, 2014. View at Publisher · View at Google Scholar · View at Scopus
  363. S. Melo, A. Villanueva, C. Moutinho et al., “Small molecule enoxacin is a cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein 2-mediated microRNA processing,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 11, pp. 4394–4399, 2011. View at Publisher · View at Google Scholar · View at Scopus
  364. N. Valeri, C. Braconi, P. Gasparini et al., “MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer,” Cancer Cell, vol. 25, no. 4, pp. 469–483, 2014. View at Publisher · View at Google Scholar · View at Scopus
  365. N. Valeri, P. Gasparini, C. Braconi et al., “MicroRNA-21 induces resistance to 5-fluorouracil by down-regulating human DNA MutS homolog 2 (hMSH2),” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 49, pp. 21098–21103, 2010. View at Publisher · View at Google Scholar · View at Scopus
  366. R. S. Geary, “Antisense oligonucleotide pharmacokinetics and metabolism,” Expert Opinion on Drug Metabolism and Toxicology, vol. 5, no. 4, pp. 381–391, 2009. View at Publisher · View at Google Scholar · View at Scopus
  367. J. Krützfeldt, N. Rajewsky, R. Braich et al., “Silencing of microRNAs in vivo with ‘antagomirs’,” Nature, vol. 438, no. 7068, pp. 685–689, 2005. View at Publisher · View at Google Scholar · View at Scopus
  368. E. van Rooij and S. Kauppinen, “Development of microRNA therapeutics is coming of age,” EMBO Molecular Medicine, vol. 6, no. 7, pp. 851–864, 2014. View at Publisher · View at Google Scholar · View at Scopus
  369. S. Obad, C. O. dos Santos, A. Petri et al., “Silencing of microRNA families by seed-targeting tiny LNAs,” Nature Genetics, vol. 43, no. 4, pp. 371–378, 2011. View at Publisher · View at Google Scholar · View at Scopus
  370. S. B. Thorsen, S. Obad, N. F. Jensen, J. Stenvang, and S. Kauppinen, “The therapeutic potential of microRNAs in cancer,” Cancer Journal, vol. 18, no. 3, pp. 275–284, 2012. View at Publisher · View at Google Scholar · View at Scopus
  371. P. Y. Chen, L. Weinmann, D. Gaidatzis et al., “Strand-specific 5′-O-methylation of siRNA duplexes controls guide strand selection and targeting specificity,” RNA, vol. 14, no. 2, pp. 263–274, 2008. View at Publisher · View at Google Scholar · View at Scopus
  372. A. G. Bader, “miR-34—a microRNA replacement therapy is headed to the clinic,” Frontiers in Genetics, vol. 3, article 120, 2012. View at Publisher · View at Google Scholar · View at Scopus
  373. A. F. Ibrahim, U. Weirauch, M. Thomas, A. Grünweller, R. K. Hartmann, and A. Aigner, “MicroRNA replacement therapy for miR-145 and miR-33a is efficacious in a model of colon carcinoma,” Cancer Research, vol. 71, no. 15, pp. 5214–5224, 2011. View at Publisher · View at Google Scholar · View at Scopus
  374. G. Liang, Y. Zhu, A. Jing et al., “Cationic microRNA-delivering nanocarriers for efficient treatment of colon carcinoma in xenograft model,” Gene Therapy, vol. 23, no. 12, pp. 829–838, 2016. View at Publisher · View at Google Scholar
  375. C. Wolfrum, S. Shi, K. N. Jayaprakash et al., “Mechanisms and optimization of in vivo delivery of lipophilic siRNAs,” Nature Biotechnology, vol. 25, no. 10, pp. 1149–1157, 2007. View at Publisher · View at Google Scholar · View at Scopus
  376. E. Wagner, “Tumor-targeted delivery of anti-microRNA for cancer therapy: PHLIP is Key,” Angewandte Chemie—International Edition, vol. 54, no. 20, pp. 5824–5826, 2015. View at Publisher · View at Google Scholar · View at Scopus
  377. T. Kawai and S. Akira, “The role of pattern-recognition receptors in innate immunity: update on toll-like receptors,” Nature Immunology, vol. 11, no. 5, pp. 373–384, 2010. View at Publisher · View at Google Scholar · View at Scopus
  378. V. Hornung, M. Guenthner-Biller, C. Bourquin et al., “Sequence-specific potent induction of IFN-α by short interfering RNA in plasmacytoid dendritic cells through TLR7,” Nature Medicine, vol. 11, no. 3, pp. 263–270, 2005. View at Publisher · View at Google Scholar · View at Scopus