Table of Contents Author Guidelines Submit a Manuscript
The Scientific World Journal
Volume 2013 (2013), Article ID 924206, 14 pages
http://dx.doi.org/10.1155/2013/924206
Review Article

MicroRNAs in Hepatocellular Carcinoma: Regulation, Function, and Clinical Implications

Laboratory of Cancer Epigenetics, Department of Medical Oncology, Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China

Received 20 December 2012; Accepted 13 January 2013

Academic Editors: H. Grønbæk, M. Ladekarl, P.-D. Line, and P. Stål

Copyright © 2013 Jie Sun 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. A. Jemal, F. Bray, M. M. Center, J. Ferlay, E. Ward, and D. Forman, “Global cancer statistics,” CA: Cancer Journal for Clinicians, vol. 61, no. 2, pp. 69–90, 2011. View at Publisher · View at Google Scholar · View at Scopus
  2. J. F. Perz, G. L. Armstrong, L. A. Farrington, Y. J. F. Hutin, and B. P. Bell, “The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide,” Journal of Hepatology, vol. 45, no. 4, pp. 529–538, 2006. View at Publisher · View at Google Scholar · View at Scopus
  3. A. J. Sanyal, S. K. Yoon, and R. Lencioni, “The etiology of hepatocellular carcinoma and consequences for treatment,” The Oncologist, vol. 15, pp. 14–22, 2010. View at Google Scholar · View at Scopus
  4. 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
  5. W. Filipowicz, S. N. Bhattacharyya, and N. Sonenberg, “Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?” Nature Reviews Genetics, vol. 9, no. 2, pp. 102–114, 2008. View at Publisher · View at Google Scholar · View at Scopus
  6. U. A. Ørom, F. C. Nielsen, and A. H. Lund, “MicroRNA-10a binds the 5UTR of ribosomal protein mRNAs and enhances their translation,” Molecular Cell, vol. 30, no. 4, pp. 460–471, 2008. View at Publisher · View at Google Scholar · View at Scopus
  7. I. Rigoutsos, “New tricks for animal micrornas: targeting of amino acid coding regions at conserved and nonconserved sites,” Cancer Research, vol. 69, no. 8, pp. 3245–3248, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. V. N. Kim, J. Han, and M. C. Siomi, “Biogenesis of small RNAs in animals,” Nature Reviews Molecular Cell Biology, vol. 10, no. 2, pp. 126–139, 2009. View at Publisher · View at Google Scholar · View at Scopus
  9. X. Cai, C. H. Hagedorn, and B. R. Cullen, “Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs,” RNA, vol. 10, no. 12, pp. 1957–1966, 2004. View at Publisher · View at Google Scholar · View at Scopus
  10. R. I. Gregory, K. P. Yan, G. Amuthan et al., “The Microprocessor complex mediates the genesis of microRNAs,” Nature, vol. 432, no. 7014, pp. 235–240, 2004. View at Publisher · View at Google Scholar · View at Scopus
  11. C. Okada, E. Yamashita, S. J. Lee et al., “A high-Resolution structure of the pre-microrna nuclear export machinery,” Science, vol. 326, no. 5957, pp. 1275–1279, 2009. View at Publisher · View at Google Scholar · View at Scopus
  12. T. P. Chendrimada, R. I. Gregory, E. Kumaraswamy et al., “TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing,” Nature, vol. 436, no. 7051, pp. 740–744, 2005. View at Publisher · View at Google Scholar · View at Scopus
  13. Y. Kim and V. N. Kim, “MicroRNA factory: RISC assembly from precursor microRNAs,” Molecular Cell, vol. 46, pp. 384–386, 2012. View at Publisher · View at Google Scholar
  14. K. Okamura, J. W. Hagen, H. Duan, D. M. Tyler, and E. C. Lai, “The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila,” Cell, vol. 130, no. 1, pp. 89–100, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. C. Ender, A. Krek, M. R. Friedländer et al., “A human snoRNA with microRNA-like functions,” Molecular Cell, vol. 32, no. 4, pp. 519–528, 2008. View at Publisher · View at Google Scholar · View at Scopus
  16. C. Cole, A. Sobala, C. Lu et al., “Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs,” RNA, vol. 15, no. 12, pp. 2147–2160, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. J. E. Babiarz, J. G. Ruby, Y. Wang, D. P. Bartel, and R. Blelloch, “Mouse ES cells express endogenous shRNAs, siRNAs, and other microprocessor-independent, dicer-dependent small RNAs,” Genes and Development, vol. 22, no. 20, pp. 2773–2785, 2008. View at Publisher · View at Google Scholar · View at Scopus
  18. D. L. Corcoran, K. V. Pandit, B. Gordon, A. Bhattacharjee, N. Kaminski, and P. V. Benos, “Features of mammalian microRNA promoters emerge from polymerase II chromatin immunoprecipitation data,” PLoS ONE, vol. 4, no. 4, Article ID e5279, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. P. K. Rao, R. M. Kumar, M. Farkhondeh, S. Baskerville, and H. F. Lodish, “Myogenic factors that regulate expression of muscle-specific microRNAs,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 23, pp. 8721–8726, 2006. View at Publisher · View at Google Scholar · View at Scopus
  20. 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
  21. N. H. Kim, H. S. Kim, N. G. Kim et al., “p53 and microRNA-34 are suppressors of canonical Wnt signaling,” Science Signaling, vol. 4, p. ra71, 2011. View at Google Scholar
  22. F. M. Sanchez-Simon, X. X. Zhang, H. H. Loh, P. Y. Law, and R. E. Rodriguez, “Morphine regulates dopaminergic neuron differentiation via miR-133b,” Molecular Pharmacology, vol. 78, no. 5, pp. 935–942, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. C. P. Bracken, P. A. Gregory, N. Kolesnikoff et al., “A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition,” Cancer Research, vol. 68, no. 19, pp. 7846–7854, 2008. View at Publisher · View at Google Scholar · View at Scopus
  24. Y. Saito, G. Liang, G. Egger et al., “Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells,” Cancer Cell, vol. 9, no. 6, pp. 435–443, 2006. View at Publisher · View at Google Scholar · View at Scopus
  25. G. K. Scott, M. D. Mattie, C. E. Berger, S. C. Benz, and C. C. Benz, “Rapid alteration of microRNA levels by histone deacetylase inhibition,” Cancer Research, vol. 66, no. 3, pp. 1277–1281, 2006. View at Publisher · View at Google Scholar · View at Scopus
  26. D. Sampath, C. Liu, K. Vasan et al., “Histone deacetylases mediate the silencing of miR-15a, miR-16, and miR-29b in chronic lymphocytic leukemia,” Blood, vol. 119, pp. 1162–1172, 2012. View at Publisher · View at Google Scholar
  27. J. M. Thomson, M. Newman, J. S. Parker, E. M. Morin-Kensicki, T. Wright, and S. M. Hammond, “Extensive post-transcriptional regulation of microRNAs and its implications for cancer,” Genes and Development, vol. 20, no. 16, pp. 2202–2207, 2006. View at Publisher · View at Google Scholar · View at Scopus
  28. J. Mineno, S. Okamoto, T. Ando et al., “The expression profile of microRNAs in mouse embryos,” Nucleic Acids Research, vol. 34, no. 6, pp. 1765–1771, 2006. View at Publisher · View at Google Scholar · View at Scopus
  29. D. R. Warner, V. Bhattacherjee, X. Yin et al., “Functional interaction between Smad, CREB binding protein, and p68 RNA helicase,” Biochemical and Biophysical Research Communications, vol. 324, no. 1, pp. 70–76, 2004. View at Publisher · View at Google Scholar · View at Scopus
  30. H. I. Suzuki, K. Yamagata, K. Sugimoto, T. Iwamoto, S. Kato, and K. Miyazono, “Modulation of microRNA processing by p53,” Nature, vol. 460, no. 7254, pp. 529–533, 2009. View at Publisher · View at Google Scholar · View at Scopus
  31. K. Yamagata, S. Fujiyama, S. Ito et al., “Maturation of microRNA is hormonally regulated by a nuclear receptor,” Molecular Cell, vol. 36, no. 2, pp. 340–347, 2009. View at Publisher · View at Google Scholar · View at Scopus
  32. N. J. Lehrbach, J. Armisen, H. L. Lightfoot et al., “LIN-28 and the poly(U) polymerase PUP-2 regulate let-7 microRNA processing in Caenorhabditis elegans,” Nature Structural and Molecular Biology, vol. 16, no. 10, pp. 1016–1020, 2009. View at Publisher · View at Google Scholar · View at Scopus
  33. N. J. Martinez and R. I. Gregory, “MicroRNA gene regulatory pathways in the establishment and maintenance of ESC identity,” Cell stem cell, vol. 7, no. 1, pp. 31–35, 2010. View at Google Scholar · View at Scopus
  34. A. Rybak, H. Fuchs, L. Smirnova et al., “A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment,” Nature Cell Biology, vol. 10, no. 8, pp. 987–993, 2008. View at Publisher · View at Google Scholar · View at Scopus
  35. H. B. El-Serag, “Epidemiology of viral hepatitis and hepatocellular carcinoma,” Gastroenterology, vol. 142, pp. 1264–1273, 2012. View at Google Scholar
  36. W. H. Liu, S. H. Yeh, and P. J. Chen, “Role of microRNAs in hepatitis B virus replication and pathogenesis,” Biochim Biophys Acta, vol. 1809, pp. 678–685, 2011. View at Google Scholar
  37. B. Wang, S. Majumder, G. Nuovo et al., “Role of microRNA-155 at early stages of hepatocarcinogenesis induced by choline-deficient and amino acid-defined diet in C57BL/6 mice,” Hepatology, vol. 50, no. 4, pp. 1152–1161, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. W. H. Liu, S. H. Yeh, C. C. Lu et al., “MicroRNA-18a prevents estrogen receptor-α expression, promoting proliferation of hepatocellular carcinoma cells,” Gastroenterology, vol. 136, no. 2, pp. 683–693, 2009. View at Publisher · View at Google Scholar · View at Scopus
  39. Y. Saito, Y. Kanai, T. Nakagawa et al., “Increased protein expression of DNA methyltransferase (DNMT) 1 is significantly correlated with the malignant potential and poor prognosis of human hepatocellular carcinomas,” International Journal of Cancer, vol. 105, no. 4, pp. 527–532, 2003. View at Publisher · View at Google Scholar · View at Scopus
  40. X. Zhang, E. Zhang, Z. Ma et al., “Modulation of hepatitis B virus replication and hepatocyte differentiation by MicroRNA-1,” Hepatology, vol. 53, no. 5, pp. 1476–1485, 2011. View at Publisher · View at Google Scholar · View at Scopus
  41. Y. Wang, Y. Lu, S. T. Toh et al., “Lethal-7 is down-regulated by the hepatitis B virus x protein and targets signal transducer and activator of transcription 3,” Journal of Hepatology, vol. 53, no. 1, pp. 57–66, 2010. View at Publisher · View at Google Scholar · View at Scopus
  42. Z. Wang, S. Lin, J. J. Li et al., “MYC protein inhibits transcription of the microRNA cluster MC-let-7a-1~let-7d via noncanonical E-box,” The Journal of Biological Chemistry, vol. 286, no. 46, pp. 39703–39714, 2011. View at Publisher · View at Google Scholar
  43. S. L. Au, C. C. Wong, J. M. Lee et al., “Enhancer of zeste homolog 2 epigenetically silences multiple tumor suppressor microRNAs to promote liver cancer metastasis,” Hepatology, vol. 56, pp. 622–631, 2012. View at Publisher · View at Google Scholar
  44. 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
  45. C. Mayr, M. T. Hemann, and D. P. Bartel, “Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation,” Science, vol. 315, no. 5818, pp. 1576–1579, 2007. View at Publisher · View at Google Scholar · View at Scopus
  46. V. B. Sampson, N. H. Rong, J. Han et al., “MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells,” Cancer Research, vol. 67, no. 20, pp. 9762–9770, 2007. View at Publisher · View at Google Scholar · View at Scopus
  47. W. Hou, Q. Tian, J. Zheng, and H. L. Bonkovsky, “MicroRNA-196 represses Bach1 protein and hepatitis C virus gene expression in human hepatoma cells expressing hepatitis C viral proteins,” Hepatology, vol. 51, no. 5, pp. 1494–1504, 2010. View at Publisher · View at Google Scholar · View at Scopus
  48. H. Yin, M. Hu, R. Zhang, Z. Shen, L. Flatow, and M. You, “MicroRNA-217 promotes ethanol-induced fat accumulation in hepatocytes by down-regulating SIRT1,” The Journal of Biological Chemistry, vol. 287, no. 13, pp. 9817–9826, 2012. View at Publisher · View at Google Scholar
  49. Y. Ladeiro, G. Couchy, C. Balabaud et al., “MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations,” Hepatology, vol. 47, no. 6, pp. 1955–1963, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. A. Dolganiuc, J. Petrasek, K. Kodys et al., “MicroRNA expression profile in lieber-decarli diet-induced alcoholic and methionine choline deficient diet-induced nonalcoholic steatohepatitis models in mice,” Alcoholism: Clinical and Experimental Research, vol. 33, no. 10, pp. 1704–1710, 2009. View at Publisher · View at Google Scholar · View at Scopus
  51. M. Vinciguerra, A. Sgroi, C. Veyrat-Durebex, L. Rubbia-Brandt, L. H. Buhler, and M. Foti, “Unsaturated fatty acids inhibit the expression of tumor suppressor phosphatase and tensin homolog(PTEN) via microRNA-21 up-regulation in hepatocytes,” Hepatology, vol. 49, no. 4, pp. 1176–1184, 2009. View at Publisher · View at Google Scholar · View at Scopus
  52. R. M. O'Connell, D. S. Rao, A. A. Chaudhuri et al., “Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder,” Journal of Experimental Medicine, vol. 205, no. 3, pp. 585–594, 2008. View at Publisher · View at Google Scholar · View at Scopus
  53. L. Xu, W. Qin, H. Zhang et al., “Alterations in microRNA expression linked to microcystin-LR-induced tumorigenicity in human WRL-68 Cells,” Mutation Research, vol. 743, pp. 75–82, 2012. View at Publisher · View at Google Scholar
  54. Y. Zhao, P. Xie, and H. Fan, “Genomic profiling of microRNAs and proteomics reveals an early molecular alteration associated with tumorigenesis induced by MC-LR in mice,” Environmental Science & Technology, vol. 46, pp. 34–41, 2012. View at Google Scholar
  55. E. Elyakim, E. Sitbon, A. Faerman et al., “hsa-miR-191 is a candidate oncogene target for hepatocellular carcinoma therapy,” Cancer Research, vol. 70, no. 20, pp. 8077–8087, 2010. View at Publisher · View at Google Scholar · View at Scopus
  56. D. Hanahan and R. A. Weinberg, “Hallmarks of cancer: the next generation,” Cell, vol. 144, no. 5, pp. 646–674, 2011. View at Publisher · View at Google Scholar · View at Scopus
  57. T. Xu, Y. Zhu, Y. Xiong, Y. Y. Ge, J. P. Yun, and S. M. Zhuang, “MicroRNA-195 suppresses tumorigenicity and regulates G1/S transition of human hepatocellular carcinoma cells,” Hepatology, vol. 50, no. 1, pp. 113–121, 2009. View at Publisher · View at Google Scholar · View at Scopus
  58. J. Kota, R. R. Chivukula, K. A. O'Donnell et al., “Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model,” Cell, vol. 137, no. 6, pp. 1005–1017, 2009. View at Publisher · View at Google Scholar · View at Scopus
  59. Y. Li, W. Tan, T. W. L. Neo et al., “Role of the miR-106b-25 microRNA cluster in hepatocellular carcinoma,” Cancer Science, vol. 100, no. 7, pp. 1234–1242, 2009. View at Publisher · View at Google Scholar · View at Scopus
  60. J. Cheng, L. Zhou, Q. F. Xie et al., “The impact of miR-34a on protein output in hepatocellular carcinoma HepG2 cells,” Proteomics, vol. 10, no. 8, pp. 1557–1572, 2010. View at Publisher · View at Google Scholar · View at Scopus
  61. Q. W. L. Wong, R. W. M. Lung, P. T. Y. Law et al., “MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin1,” Gastroenterology, vol. 135, no. 1, pp. 257–269, 2008. View at Publisher · View at Google Scholar · View at Scopus
  62. C. Xu, S. Liu, H. Fu et al., “MicroRNA-193b regulates proliferation, migration and invasion in human hepatocellular carcinoma cells,” European Journal of Cancer, vol. 46, no. 15, pp. 2828–2836, 2010. View at Publisher · View at Google Scholar · View at Scopus
  63. W. Zhang, G. Kong, J. Zhang, T. Wang, L. Ye, and X. Zhang, “MicroRNA-520b inhibits growth of hepatoma cells by targeting MEKK2 and cyclin D1,” PLoS ONE, vol. 7, Article ID e31450, 2012. View at Google Scholar
  64. L. Gramantieri, F. Fornari, M. Ferracin et al., “MicroRNA-221 targets Bmf in hepatocellular carcinoma and correlates with tumor multifocality,” Clinical Cancer Research, vol. 15, no. 16, pp. 5073–5081, 2009. View at Publisher · View at Google Scholar · View at Scopus
  65. A. D. Sharma, N. Narain, E. M. Händel et al., “MicroRNA-221 regulates FAS-induced fulminant liver failure,” Hepatology, vol. 53, no. 5, pp. 1651–1661, 2011. View at Publisher · View at Google Scholar · View at Scopus
  66. A. Zhao, Q. Zeng, X. Xie et al., “MicroRNA-125b induces cancer cell apoptosis through suppression of Bcl-2 expression,” Journal of Genetics and Genomics, vol. 39, pp. 29–35, 2012. View at Publisher · View at Google Scholar
  67. J. Gong, J. P. Zhang, B. Li et al., “MicroRNA-125b promotes apoptosis by regulating the expression of Mcl-1, Bcl-w and IL-6R,” Oncogene, 2012. View at Publisher · View at Google Scholar
  68. Y. Zhang, S. Takahashi, A. Tasaka, T. Yoshima, H. Ochi, and K. Chayama, “Involvement of microRNA-224 in cell proliferation, migration, invasion and anti-apoptosis in hepatocellular carcinoma,” Journal of Gastroenterology and Hepatology, 2012. View at Publisher · View at Google Scholar
  69. Y. Xiong, J. H. Fang, J. P. Yun et al., “Effects of microrna-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma,” Hepatology, vol. 51, no. 3, pp. 836–845, 2010. View at Publisher · View at Google Scholar · View at Scopus
  70. H. Su, J. R. Yang, T. Xu et al., “MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity,” Cancer Research, vol. 69, no. 3, pp. 1135–1142, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. C. J. F. Lin, H. Y. Gong, H. C. Tseng, W. L. Wang, and J. L. Wu, “miR-122 targets an anti-apoptotic gene, Bcl-w, in human hepatocellular carcinoma cell lines,” Biochemical and Biophysical Research Communications, vol. 375, no. 3, pp. 315–320, 2008. View at Publisher · View at Google Scholar · View at Scopus
  72. M. Garofalo, G. Di Leva, G. Romano et al., “miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation,” Cancer Cell, vol. 16, no. 6, pp. 498–509, 2009. View at Publisher · View at Google Scholar · View at Scopus
  73. S. Shimizu, T. Takehara, H. Hikita et al., “The let-7 family of microRNAs inhibits Bcl-xL expression and potentiates sorafenib-induced apoptosis in human hepatocellular carcinoma,” Journal of Hepatology, vol. 52, no. 5, pp. 698–704, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. K. Wu, J. Ding, C. Chen et al., “Hepatic transforming growth factor beta gives rise to tumor-initiating cells and promotes liver cancer development,” Hepatology, vol. 56, pp. 2255–2267, 2012. View at Publisher · View at Google Scholar
  75. F. Meng, R. Henson, H. Wehbe-Janek, K. Ghoshal, S. T. Jacob, and T. Patel, “MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer,” Gastroenterology, vol. 133, no. 2, pp. 647–658, 2007. View at Publisher · View at Google Scholar · View at Scopus
  76. K. Yuan, Z. Lian, B. Sun, M. M. Clayton, I. O. Ng, and M. A. Feitelson, “Role of miR-148a in hepatitis B associated hepatocellular carcinoma,” PLoS ONE, vol. 7, no. 4, Article ID e35331, 2012. View at Publisher · View at Google Scholar
  77. F. Fornari, M. Milazzo, P. Chieco et al., “In hepatocellular carcinoma miR-519d is up-regulated by p53 and DNA hypomethylation and targets CDKN1A/p21, PTEN, AKT3 and TIMP2,” The Journal of Pathology, vol. 227, pp. 275–285, 2012. View at Publisher · View at Google Scholar
  78. G. Kong, J. Zhang, S. Zhang, C. Shan, L. Ye, and X. Zhang, “Upregulated microRNA-29a by hepatitis B virus X protein enhances hepatoma cell migration by targeting PTEN in cell culture model,” PLoS ONE, vol. 6, no. 5, Article ID e19518, 2011. View at Publisher · View at Google Scholar · View at Scopus
  79. Y. Fang, J. L. Xue, Q. Shen, J. Chen, and L. Tian, “MicroRNA-7 inhibits tumor growth and metastasis by targeting the phosphoinositide 3-kinase/Akt pathway in hepatocellular carcinoma,” Hepatology, vol. 55, pp. 1852–1862, 2012. View at Publisher · View at Google Scholar
  80. F. Fornari, M. Milazzo, P. Chieco et al., “MiR-199a-3p regulates mTOR and c-Met to influence the doxorubicin sensitivity of human hepatocarcinoma cells,” Cancer Research, vol. 70, no. 12, pp. 5184–5193, 2010. View at Publisher · View at Google Scholar · View at Scopus
  81. A. Salvi, C. Sabelli, S. Moncini et al., “MicroRNA-23b mediates urokinase and c-met downmodulation and a decreased migration of human hepatocellular carcinoma cells,” FEBS Journal, vol. 276, no. 11, pp. 2966–2982, 2009. View at Publisher · View at Google Scholar · View at Scopus
  82. J. Datta, H. Kutay, M. W. Nasser et al., “Methylation mediated silencing of microRNA-1 gene and its role in hepatocellular carcinogenesis,” Cancer Research, vol. 68, no. 13, pp. 5049–5058, 2008. View at Publisher · View at Google Scholar · View at Scopus
  83. S. Tan, R. Li, K. Ding, P. E. Lobie, and T. Zhu, “MiR-198 inhibits migration and invasion of hepatocellular carcinoma cells by targeting the HGF/c-MET pathway,” FEBS Letters, vol. 585, no. 14, pp. 2229–2234, 2011. View at Publisher · View at Google Scholar · View at Scopus
  84. R. Buurman, E. Gurlevik, V. Schaffer et al., “Histone deacetylases activate hepatocyte growth factor signaling by repressing microRNA-449 in hepatocellular carcinoma cells,” Gastroenterology, vol. 143, pp. 811–820, 2012. View at Google Scholar
  85. N. Li, H. Fu, Y. Tie et al., “miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells,” Cancer Letters, vol. 275, no. 1, pp. 44–53, 2009. View at Publisher · View at Google Scholar · View at Scopus
  86. P. K. Santhekadur, S. K. Das, R. Gredler et al., “Multifunction protein staphylococcal nuclease domain containing 1 (SND1) promotes tumor angiogenesis in human hepatocellular carcinoma through novel pathway that involves nuclear factor κB and miR-221,” The Journal of Biological Chemistry, vol. 287, no. 17, pp. 13952–13958, 2012. View at Publisher · View at Google Scholar
  87. T. C. Shih, Y. J. Tien, C. J. Wen et al., “MicroRNA-214 downregulation contributes to tumor angiogenesis by inducing secretion of the hepatoma-derived growth factor in human hepatoma,” Journal of Hepatology, vol. 57, no. 3, pp. 584–591, 2012. View at Publisher · View at Google Scholar
  88. W. C. Tsai, P. W. C. Hsu, T. C. Lai et al., “MicroRNA-122, a tumor suppressor MicroRNA that regulates intrahepatic metastasis of hepatocellular carcinoma,” Hepatology, vol. 49, no. 5, pp. 1571–1582, 2009. View at Publisher · View at Google Scholar · View at Scopus
  89. J. H. Fang, H. C. Zhou, C. Zeng et al., “MicroRNA-29b suppresses tumor angiogenesis, invasion, and metastasis by regulating matrix metalloproteinase 2 expression,” Hepatology, vol. 54, pp. 1729–1740, 2011. View at Google Scholar
  90. G. Alpini, S. S. Glaser, J. P. Zhang et al., “Regulation of placenta growth factor by microRNA-125b in hepatocellular cancer,” Journal of Hepatology, vol. 55, pp. 1339–1345, 2011. View at Google Scholar
  91. W. P. Tsang and T. T. Kwok, “Let-7a microRNA suppresses therapeutics-induced cancer cell death by targeting caspase-3,” Apoptosis, vol. 13, no. 10, pp. 1215–1222, 2008. View at Publisher · View at Google Scholar · View at Scopus
  92. P. Di Fazio, R. Montalbano, D. Neureiter et al., “Downregulation of HMGA2 by the pan-deacetylase inhibitor panobinostat is dependent on hsa-let-7b expression in liver cancer cell lines,” Experimental Cell Research, vol. 318, pp. 1832–1843, 2012. View at Google Scholar
  93. X. M. Zhu, L. J. Wu, J. Xu, R. Yang, and F. S. Wu, “Let-7c microRNA expression and clinical significance in hepatocellular carcinoma,” The Journal of International Medical Research, vol. 39, pp. 2323–2329, 2011. View at Google Scholar
  94. Y. M. Shah, K. Morimura, Q. Yang, T. Tanabe, M. Takagi, and F. J. Gonzalez, “Peroxisome proliferator-activated receptor α regulates a microRNA-mediated signaling cascade responsible for hepatocellular proliferation,” Molecular and Cellular Biology, vol. 27, no. 12, pp. 4238–4247, 2007. View at Publisher · View at Google Scholar · View at Scopus
  95. J. Ji, L. Zhao, A. Budhu et al., “Let-7g targets collagen type I α2 and inhibits cell migration in hepatocellular carcinoma,” Journal of Hepatology, vol. 52, no. 5, pp. 690–697, 2010. View at Publisher · View at Google Scholar · View at Scopus
  96. F. F. Lan, H. Wang, Y. C. Chen et al., “Hsa-let-7g inhibits proliferation of hepatocellular carcinoma cells by downregulation of c-Myc and upregulation of p16INK4A,” International Journal of Cancer, vol. 128, no. 2, pp. 319–331, 2011. View at Publisher · View at Google Scholar · View at Scopus
  97. D. Li, P. Yang, H. Li et al., “MicroRNA-1 inhibits proliferation of hepatocarcinoma cells by targeting endothelin-1,” Life Sciences, vol. 91, pp. 440–447, 2012. View at Google Scholar
  98. X. Wei, T. Xiang, G. Ren et al., “miR-101 is down-regulated by the hepatitis B virus x protein and induces aberrant DNA methylation by targeting DNA methyltransferase 3A,” Cell Signal, vol. 25, pp. 439–446, 2012. View at Google Scholar
  99. Y. Zhang, X. Guo, L. Xiong et al., “MicroRNA-101 suppresses SOX9-dependent tumorigenicity and promotes favorable prognosis of human hepatocellular carcinoma,” FEBS Letters, vol. 586, no. 24, pp. 4362–4370, 2012. View at Publisher · View at Google Scholar
  100. H. V. Reddi, P. Madde, D. Milosevic et al., “The putative PAX8/PPARγ fusion oncoprotein exhibits partial tumor suppressor activity through up-regulation of Micro-RNA-122 and dominant-negative PPARγ activity,” Genes and Cancer, vol. 2, no. 1, pp. 46–55, 2011. View at Publisher · View at Google Scholar · View at Scopus
  101. J. Xu, X. Zhu, L. Wu et al., “MicroRNA-122 suppresses cell proliferation and induces cell apoptosis in hepatocellular carcinoma by directly targeting Wnt/β-catenin pathway,” Liver International, vol. 32, no. 5, pp. 752–760, 2012. View at Publisher · View at Google Scholar
  102. Q. Lang and C. Ling, “MiR-124 suppresses cell proliferation in hepatocellular carcinoma by targeting PIK3CA,” Biochemical and Biophysical Research Communications, vol. 426, pp. 247–252, 2012. View at Google Scholar
  103. Q. Bi, S. Tang, L. Xia et al., “Ectopic expression of MiR-125a inhibits the proliferation and metastasis of hepatocellular carcinoma by targeting MMP11 and VEGF,” PLoS ONE, vol. 7, no. 6, Article ID e40169, 2012. View at Publisher · View at Google Scholar
  104. J. K. Kim, J. H. Noh, K. H. Jung et al., “SIRT7 oncogenic potential in human hepatocellular carcinoma and its regulation by the tumor suppressors mir-125a-5p and mir-125b,” Hepatology, 2012. View at Publisher · View at Google Scholar
  105. L. Liang, C. M. Wong, Q. Ying et al., “MicroRNA-125b suppressesed human liver cancer cell proliferation and metastasis by directly targeting oncogene LIN28B2,” Hepatology, vol. 52, no. 5, pp. 1731–1740, 2010. View at Publisher · View at Google Scholar · View at Scopus
  106. D. N. Fan, F. H. Tsang, A. H. Tam et al., “Histone lysine methyltransferase, suppressor of variegation 3-9 homolog 1, promotes hepatocellular carcinoma progression and is negatively regulated by microRNA-125b,” Hepatology, 2012. View at Publisher · View at Google Scholar
  107. C. C. Wong, C. Wong, E. K. Tung et al., “The MicroRNA miR-139 suppresses metastasis and progression of hepatocellular carcinoma by down-regulating rho-kinase 2,” Gastroenterology, vol. 140, no. 1, pp. 322–331, 2011. View at Publisher · View at Google Scholar · View at Scopus
  108. Q. Fan, M. He, X. Deng et al., “Derepression of c-Fos caused by MicroRNA-139 down-regulation contributes to the metastasis of human hepatocellular carcinoma,” Cell Biochemistry and Function, 2012. View at Publisher · View at Google Scholar
  109. W. Wang, L. J. Zhao, Y. X. Tan, H. Ren, and Z. T. Qi, “MiR-138 induces cell cycle arrest by targeting cyclin D3 in hepatocellular carcinoma,” Carcinogenesis, vol. 33, pp. 1113–1120, 2012. View at Google Scholar
  110. P. T. Law, A. K. Ching, A. W. Chan et al., “MiR-145 modulates multiple components of the insulin-like growth factor pathway in hepatocellular carcinoma,” Carcinogenesis, vol. 33, pp. 1134–1141, 2012. View at Google Scholar
  111. Y. Jia, H. Liu, Q. Zhuang et al., “Tumorigenicity of cancer stem-like cells derived from hepatocarcinoma is regulated by microRNA-145,” Oncology Reports, vol. 27, pp. 1865–1872, 2012. View at Google Scholar
  112. X. Yang, J. Yu, J. Yin, Q. Xiang, H. Tang, and X. Lei, “MiR-195 regulates cell apoptosis of human hepatocellular carcinoma cells by targeting LATS2,” Pharmazie, vol. 67, pp. 645–651, 2012. View at Google Scholar
  113. J. Hou, L. Lin, W. Zhou et al., “Identification of miRNomes in human liver and hepatocellular carcinoma reveals miR-199a/b-3p as therapeutic target for hepatocellular carcinoma,” Cancer Cell, vol. 19, no. 2, pp. 232–243, 2011. View at Publisher · View at Google Scholar · View at Scopus
  114. T. Shatseva, D. Y. Lee, Z. Deng, and B. B. Yang, “MicroRNA miR-199a-3p regulates cell proliferation and survival by targeting caveolin-2,” Journal of Cell Science, vol. 124, no. 16, pp. 2826–2836, 2011. View at Publisher · View at Google Scholar · View at Scopus
  115. Q. Shen, V. R. Cicinnati, X. Zhang et al., “Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion,” Molecular Cancer, vol. 9, article 227, 2010. View at Publisher · View at Google Scholar · View at Scopus
  116. N. Xu, J. Zhang, C. Shen et al., “Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell,” Biochemical and Biophysical Research Communications, vol. 423, pp. 826–831, 2012. View at Google Scholar
  117. J. H. Yuan, F. Yang, B. F. Chen et al., “The histone deacetylase 4/SP1/microrna-200a regulatory network contributes to aberrant histone acetylation in hepatocellular carcinoma,” Hepatology, vol. 54, pp. 2025–2035, 2011. View at Google Scholar
  118. W. Wei, L. Wanjun, S. Hui, C. Dongyue, Y. Xinjun, and Z. Jisheng, “miR-203 inhibits proliferation of HCC cells by targeting survivin,” Cell Biochemistry and Function, vol. 31, no. 1, pp. 82–85, 2012. View at Publisher · View at Google Scholar
  119. X. Wang, J. Chen, F. Li et al., “MiR-214 inhibits cell growth in hepatocellular carcinoma through suppression of β-catenin,” Biochemical and Biophysical Research Communications, vol. 428, no. 4, pp. 525–531, 2012. View at Publisher · View at Google Scholar
  120. H. Xia, L. L. Ooi, and K. M. Hui, “MiR-214 targets β-catenin pathway to suppress invasion, stem-like traits and recurrence of human hepatocellular carcinoma,” PLoS ONE, vol. 7, no. 9, Article ID e44206, 2012. View at Publisher · View at Google Scholar
  121. N. Huang, J. Lin, J. Ruan et al., “MiR-219-5p inhibits hepatocellular carcinoma cell proliferation by targeting glypican-3,” FEBS Letters, vol. 586, pp. 884–891, 2012. View at Google Scholar
  122. Y. Zhu, Y. Lu, Q. Zhang et al., “MicroRNA-26a/b and their host genes cooperate to inhibit the G1/S transition by activating the pRb protein,” Nucleic Acids Research, vol. 40, pp. 4615–4625, 2012. View at Google Scholar
  123. X. C. Zhu, Q. Z. Dong, X. F. Zhang et al., “microRNA-29a suppresses cell proliferation by targeting SPARC in hepatocellular carcinoma,” International Journal of Molecular Medicine, vol. 30, no. 6, pp. 1321–1326, 2012. View at Publisher · View at Google Scholar
  124. P. Yang, Q. J. Li, Y. Feng et al., “TGF-β-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma,” Cancer Cell, vol. 22, pp. 291–303, 2012. View at Publisher · View at Google Scholar
  125. Y. Chang, W. Yan, X. He et al., “miR-375 inhibits autophagy and reduces viability of hepatocellular carcinoma cells under hypoxic conditions,” Gastroenterology, vol. 143, pp. 177–187, 2012. View at Google Scholar
  126. Y. Zheng, L. Yin, H. Chen et al., “miR-376a suppresses proliferation and induces apoptosis in hepatocellular carcinoma,” FEBS Letters, vol. 586, pp. 2396–2403, 2012. View at Google Scholar
  127. Z. Weng, D. Wang, W. Zhao et al., “microRNA-450a targets DNA methyltransferase 3a in hepatocellular carcinoma,” Experimental and Therapeutic Medicine, vol. 2, no. 5, pp. 951–955, 2011. View at Publisher · View at Google Scholar · View at Scopus
  128. Y. Yan, Y. C. Luo, H. Y. Wan et al., “MicroRNA-10a is involved in the metastatic process by regulating Eph tyrosine kinase receptor A4-Mediated epithelial-mesenchymal transition and adhesion in hepatoma cells,” Hepatology, 2012. View at Publisher · View at Google Scholar
  129. Q. J. Li, L. Zhou, F. Yang et al., “MicroRNA-10b promotes migration and invasion through CADM1 in human hepatocellular carcinoma cells,” Tumour Biology, vol. 33, no. 5, pp. 1455–1465, 2012. View at Publisher · View at Google Scholar
  130. N. Xu, C. Shen, Y. Luo et al., “Upregulated miR-130a increases drug resistance by regulating RUNX3 and Wnt signaling in cisplatin-treated HCC cell,” Biochemical and Biophysical Research Communications, vol. 425, pp. 468–472, 2012. View at Google Scholar
  131. S. Liu, W. Guo, J. Shi et al., “MicroRNA-135a contributes to the development of portal vein tumor thrombus by promoting metastasis in hepatocellular carcinoma,” Journal of Hepatology, vol. 56, pp. 389–396, 2012. View at Google Scholar
  132. X. Zhang, S. Liu, T. Hu, S. Liu, Y. He, and S. Sun, “Up-regulated microRNA-143 transcribed by nuclear factor kappa B enhances hepatocarcinoma metastasis by repressing fibronectin expression,” Hepatology, vol. 50, no. 2, pp. 490–499, 2009. View at Publisher · View at Google Scholar · View at Scopus
  133. Y. Zhang, W. Wei, N. Cheng et al., “Hepatitis C virus-induced up-regulation of microRNA-155 promotes hepatocarcinogenesis by activating Wnt signaling,” Hepatology, vol. 56, pp. 1631–1640, 2012. View at Google Scholar
  134. B. Wang, S. H. Hsu, S. Majumder et al., “TGFβ-mediated upregulation of hepatic miR-181b promotes hepatocarcinogenesis by targeting TIMP3,” Oncogene, vol. 29, no. 12, pp. 1787–1797, 2010. View at Publisher · View at Google Scholar · View at Scopus
  135. J. Wang, J. Li, J. Shen, C. Wang, L. Yang, and X. Zhang, “MicroRNA-182 downregulates metastasis suppressor 1 and contributes to metastasis of hepatocellular carcinoma,” BMC Cancer, vol. 12, p. 227, 2012. View at Google Scholar
  136. Y. Tomimaru, H. Eguchi, H. Nagano et al., “MicroRNA-21 induces resistance to the anti-tumour effect of interferon-α/5-fluorouracil in hepatocellular carcinoma cells,” British Journal of Cancer, vol. 103, no. 10, pp. 1617–1626, 2010. View at Publisher · View at Google Scholar · View at Scopus
  137. E. C. Connolly, K. Van Doorslaer, L. E. Rogler, and C. E. Rogler, “Overexpression of miR-21 promotes an in vitro metastatic phenotype by targeting the tumor suppressor RHOB,” Molecular Cancer Research, vol. 8, no. 5, pp. 691–700, 2010. View at Publisher · View at Google Scholar · View at Scopus
  138. Q. Zhu, Z. Wang, Y. Hu et al., “miR-21 promotes migration and invasion by the miR-21-PDCD4-AP-1 feedback loop in human hepatocellular carcinoma,” Oncology Reports, vol. 27, pp. 1660–1668, 2012. View at Google Scholar
  139. Q. Ying, L. Liang, W. Guo et al., “Hypoxia-inducible microRNA-210 augments the metastatic potential of tumor cells by targeting vacuole membrane protein 1 in hepatocellular carcinoma,” Hepatology, vol. 54, pp. 2064–2075, 2011. View at Google Scholar
  140. W. Yang, T. Sun, J. Cao, F. Liu, Y. Tian, and W. Zhu, “Downregulation of miR-210 expression inhibits proliferation, induces apoptosis and enhances radiosensitivity in hypoxic human hepatoma cells in vitro,” Experimental Cell Research, vol. 318, pp. 944–954, 2012. View at Google Scholar
  141. P. J. Chen, S. H. Yeh, W. H. Liu et al., “Androgen pathway stimulates microRNA-216a transcription to suppress the tumor suppressor in lung cancer-1 gene in early hepatocarcinogenesis,” Hepatology, vol. 56, pp. 632–643, 2012. View at Google Scholar
  142. F. Fornari, L. Gramantieri, M. Ferracin et al., “MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma,” Oncogene, vol. 27, no. 43, pp. 5651–5661, 2008. View at Publisher · View at Google Scholar · View at Scopus
  143. P. Pineau, S. Volinia, K. McJunkin et al., “miR-221 overexpression contributes to liver tumorigenesis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 1, pp. 264–269, 2010. View at Publisher · View at Google Scholar · View at Scopus
  144. Q. Yuan, K. Loya, B. Rani et al., “MicroRNA-221 overexpression accelerates hepatocyte proliferation during liver regeneration,” Hepatology, vol. 57, no. 1, pp. 299–310, 2012. View at Publisher · View at Google Scholar
  145. M. Notarbartolo, L. Giannitrapani, N. Vivona et al., “Frequent alteration of the Yin Yang 1/Raf-1 Kinase inhibitory protein ratio in hepatocellular carcinoma,” OMICS A Journal of Integrative Biology, vol. 15, no. 5, pp. 267–272, 2011. View at Publisher · View at Google Scholar · View at Scopus
  146. Y. Wang, H. C. Toh, P. Chow et al., “MicroRNA-224 is up-regulated in hepatocellular carcinoma through epigenetic mechanisms,” The FASEB Journal, vol. 26, pp. 3032–3041, 2012. View at Google Scholar
  147. C. Scisciani, S. Vossio, F. Guerrieri et al., “Transcriptional regulation of miR-224 upregulated in human HCCs by NFκB inflammatory pathways,” Journal of Hepatology, vol. 56, no. 4, pp. 855–861, 2012. View at Publisher · View at Google Scholar
  148. Y. Wang, A. T. C. Lee, J. Z. I. Ma et al., “Profiling microRNA expression in hepatocellular carcinoma reveals microRNA-224 up-regulation and apoptosis inhibitor-5 as a microRNA-224-specific target,” Journal of Biological Chemistry, vol. 283, no. 19, pp. 13205–13215, 2008. View at Publisher · View at Google Scholar · View at Scopus
  149. B. Wang, S. H. Hsu, W. Frankel, K. Ghoshal, and S. T. Jacob, “Stat3-mediated activation of microRNA-23a suppresses gluconeogenesis in hepatocellular carcinoma by down-regulating glucose-6-phosphatase and peroxisome proliferator-activated receptor gamma, coactivator 1 alpha,” Hepatology, vol. 56, pp. 186–197, 2012. View at Publisher · View at Google Scholar
  150. N. Wu, X. Liu, X. Xu et al., “MicroRNA-373, a new regulator of protein phosphatase 6, functions as an oncogene in hepatocellular carcinoma,” FEBS Journal, vol. 278, no. 12, pp. 2044–2054, 2011. View at Publisher · View at Google Scholar · View at Scopus
  151. P. Zhou, W. Jiang, L. Wu, R. Chang, K. Wu, and Z. Wang, “miR-301a is a candidate oncogene that targets the homeobox gene Gax in human hepatocellular carcinoma,” Digestive Diseases and Sciences, vol. 57, pp. 1171–1180, 2012. View at Google Scholar
  152. L. Y. Zhang, M. Liu, X. Li, and H. Tang, “MiR-490-3p modulates cell growth and epithelial to mesenchymal transition of hepatocellular carcinoma cells by targeting endoplasmic reticulum-Golgi intermediate compartment protein 3(ERGIC3),” The Journal of Biological Chemistry, 2012. View at Publisher · View at Google Scholar
  153. Q. Tian, L. Liang, J. Ding et al., “MicroRNA-550a acts as a pro-metastatic gene and directly targets cytoplasmic polyadenylation element-binding protein 4 in hepatocellular carcinoma,” PLoS ONE, vol. 7, no. 11, Article ID e48958, 2012. View at Publisher · View at Google Scholar
  154. X. Jiang, G. Xiang, Y. Wang et al., “MicroRNA-590-5p regulates proliferation and invasion in human hepatocellular carcinoma cells by targeting TGF-β RII,” Molecules and Cells, vol. 33, no. 6, pp. 545–551, 2012. View at Publisher · View at Google Scholar
  155. H. M. El Tayebi, K. A. Hosny, G. Esmat, K. Breuhahn, and A. I. Abdelaziz, “miR-615-5p is restrictedly expressed in cirrhotic and cancerous liver tissues and its overexpression alleviates the tumorigenic effects in hepatocellular carcinoma,” FEBS Letters, vol. 586, pp. 3309–3316, 2012. View at Google Scholar
  156. L. Zhang, L. Yang, X. Liu et al., “MiR-657 promotes tumorigenesis in hepatocellular carcinoma by targeting transducin-like enhancer protein 1 through NF-κB pathways,” Hepatology, 2012. View at Publisher · View at Google Scholar
  157. M. S. Kwak, D. H. Lee, Y. Cho et al., “Association of polymorphism in pri-microRNAs-371-372-373 with the occurrence of hepatocellular carcinoma in hepatitis B virus infected patients,” PLoS ONE, vol. 7, Article ID e41983, 2012. View at Google Scholar
  158. J. S. Bae, J. H. Kim, C. F. Pasaje et al., “Association study of genetic variations in microRNAs with the risk of hepatitis B-related liver diseases,” Digestive and Liver Disease, vol. 44, pp. 849–854, 2012. View at Google Scholar
  159. W. H. Kim, K. T. Min, Y. J. Jeon et al., “Association study of microRNA polymorphisms with hepatocellular carcinoma in Korean population,” Gene, vol. 504, pp. 92–97, 2012. View at Google Scholar
  160. H. Akkiz, S. Bayram, A. Bekar, E. Akgollu, and O. Uskudar, “Genetic variation in the microRNA-499 gene and hepatocellular carcinoma risk in a Turkish population: lack of any association in a case-control study,” Asian Pacific Journal of Cancer Prevention, vol. 12, pp. 3107–3112, 2011. View at Google Scholar
  161. Y. Xiang, S. Fan, J. Cao, S. Huang, and L. P. Zhang, “Association of the microRNA-499 variants with susceptibility to hepatocellular carcinoma in a Chinese population,” Molecular Biology Reports, vol. 39, pp. 7019–7023, 2012. View at Google Scholar
  162. Y. Xu, L. Liu, J. Liu et al., “A potentially functional polymorphism in the promoter region of miR-34b/c is associated with an increased risk for primary hepatocellular carcinoma,” International Journal of Cancer, vol. 128, no. 2, pp. 412–417, 2011. View at Publisher · View at Google Scholar · View at Scopus
  163. J. Guo, M. Jin, M. Zhang, and K. Chen, “A genetic variant in miR-196a2 increased digestive system cancer risks: a meta-analysis of 15 case-control studies,” PLoS ONE, vol. 7, no. 1, Article ID e30585, 2012. View at Publisher · View at Google Scholar
  164. X. D. Li, Z. G. Li, X. X. Song, and C. F. Liu, “A variant in microRNA-196a2 is associated with susceptibility to hepatocellular carcinoma in Chinese patients with cirrhosis,” Pathology, vol. 42, no. 7, pp. 669–673, 2010. View at Publisher · View at Google Scholar · View at Scopus
  165. H. Akkaz, S. Bayram, A. Bekar, E. Akgöllü, and Y. Ülger, “A functional polymorphism in pre-microRNA-196a-2 contributes to the susceptibility of hepatocellular carcinoma in a Turkish population: a case-control study,” Journal of Viral Hepatitis, vol. 18, no. 7, pp. e399–e407, 2011. View at Publisher · View at Google Scholar · View at Scopus
  166. H. Akkiz, S. Bayram, A. Bekar, E. Akgollu, O. Uskudar, and M. Sandikci, “No association of pre-microRNA-146a rs2910164 polymorphism and risk of hepatocellular carcinoma development in Turkish population: a case-control study,” Gene, vol. 486, pp. 104–109, 2011. View at Google Scholar
  167. Y. Liu, Y. Zhang, J. Wen et al., “A genetic variant in the promoter region of miR-106b-25 cluster and risk of HBV infection and hepatocellular carcinoma,” PLoS ONE, vol. 7, Article ID e32230, 2012. View at Google Scholar
  168. Y. Gao, Y. He, J. Ding et al., “An insertion/deletion polymorphism at miRNA-122-binding site in the interleukin-1a 3α untranslated region confers risk for hepatocellular carcinoma,” Carcinogenesis, vol. 30, no. 12, pp. 2064–2069, 2009. View at Publisher · View at Google Scholar · View at Scopus
  169. S. Chen, Y. He, J. Ding et al., “An insertion/deletion polymorphism in the 3′ untranslated region of β-transducin repeat-containing protein (βTrCP) is associated with susceptibility for hepatocellular carcinoma in Chinese,” Biochemical and Biophysical Research Communications, vol. 391, no. 1, pp. 552–556, 2010. View at Publisher · View at Google Scholar · View at Scopus
  170. C. Zhou, Q. Yu, L. Chen, J. Wang, S. Zheng, and J. Zhang, “A miR-1231 binding site polymorphism in the 3UTR of IFNAR1 is associated with hepatocellular carcinoma susceptibility,” Gene, vol. 507, pp. 95–98, 2012. View at Google Scholar
  171. Q. Yu, C. X. Zhou, N. S. Chen, S. D. Zheng, L. M. Shen, and J. K. Zhang, “A polymorphism within ErbB4 is associated with risk for hepatocellular carcinoma in Chinese population,” World Journal of Gastroenterology, vol. 18, pp. 383–387, 2012. View at Google Scholar
  172. Z. Zhu, Y. Jiang, S. Chen et al., “An insertion/deletion polymorphism in the 3' untranslated region of type I collagen a2 (COL1A2) is associated with susceptibility for hepatocellular carcinoma in a Chinese population,” Cancer Genetics, vol. 204, pp. 265–269, 2011. View at Google Scholar
  173. F. Zheng, Y. J. Liao, M. Y. Cai et al., “The putative tumour suppressor microRNA-124 modulates hepatocellular carcinoma cell aggressiveness by repressing ROCK2 and EZH2,” Gut, vol. 61, pp. 278–289, 2012. View at Google Scholar
  174. T. Kim, A. Veronese, F. Pichiorri et al., “p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2,” Journal of Experimental Medicine, vol. 208, no. 5, pp. 875–883, 2011. View at Publisher · View at Google Scholar · View at Scopus
  175. S. Toffanin, Y. Hoshida, A. Lachenmayer et al., “MicroRNA-based classification of hepatocellular carcinoma and oncogenic role of miR-517a,” Gastroenterology, vol. 140, no. 5, pp. 1618–1628, 2011. View at Publisher · View at Google Scholar · View at Scopus
  176. Y. Murakami, T. Yasuda, K. Saigo et al., “Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues,” Oncogene, vol. 25, no. 17, pp. 2537–2545, 2006. View at Publisher · View at Google Scholar · View at Scopus
  177. C. Augello, V. Vaira, L. Caruso et al., “MicroRNA profiling of hepatocarcinogenesis identifies C19MC cluster as a novel prognostic biomarker in hepatocellular carcinoma,” Liver International, vol. 32, pp. 772–782, 2012. View at Google Scholar
  178. Q. W. L. Wong, A. K. K. Ching, A. W. H. Chan et al., “MiR-222 overexpression confers cell migratory advantages in hepatocellular carcinoma through enhancing AKT signaling,” Clinical Cancer Research, vol. 16, no. 3, pp. 867–875, 2010. View at Publisher · View at Google Scholar · View at Scopus
  179. C. Coulouarn, V. M. Factor, J. B. Andersen, M. E. Durkin, and S. S. Thorgeirsson, “Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties,” Oncogene, vol. 28, no. 40, pp. 3526–3536, 2009. View at Publisher · View at Google Scholar · View at Scopus
  180. C. Wang, B. Song, W. Song et al., “Underexpressed microRNA-199b-5p targets hypoxia-inducible factor-1α in hepatocellular carcinoma and predicts prognosis of hepatocellular carcinoma patients,” Journal of Gastroenterology and Hepatology, vol. 26, pp. 1630–1637, 2011. View at Publisher · View at Google Scholar
  181. J. Zhang, Y. Yang, T. Yang et al., “MicroRNA-22, downregulated in hepatocellular carcinoma and correlated with prognosis, suppresses cell proliferation and tumourigenicity,” British Journal of Cancer, vol. 103, no. 8, pp. 1215–1220, 2010. View at Publisher · View at Google Scholar · View at Scopus
  182. J. Ji, J. Shi, A. Budhu et al., “MicroRNA expression, survival, and response to interferon in liver cancer,” The New England Journal of Medicine, vol. 361, pp. 1437–1447, 2009. View at Google Scholar
  183. D. Li, X. Liu, L. Lin et al., “MicroRNA-99a inhibits hepatocellular carcinoma growth and correlates with prognosis of patients with hepatocellular carcinoma,” The Journal of Biological Chemistry, vol. 286, no. 42, pp. 36677–36685, 2011. View at Publisher · View at Google Scholar
  184. W. Li, L. Xie, X. He et al., “Diagnostic and prognostic implications of microRNAs in human hepatocellular carcinoma,” International Journal of Cancer, vol. 123, no. 7, pp. 1616–1622, 2008. View at Publisher · View at Google Scholar · View at Scopus
  185. L. Chen, M. Jiang, W. Yuan, and H. Tang, “miR-17-5p as a novel prognostic marker for hepatocellular carcinoma,” Journal of Investigative Surgery, vol. 25, pp. 156–161, 2012. View at Google Scholar
  186. J. Zheng, P. Dong, S. Gao, N. Wang, and F. Yu, “High expression of serum miR-17-5p associated with poor prognosis in patients with hepatocellular carcinoma,” Hepatogastroenterology, vol. 60, no. 123, 2012. View at Publisher · View at Google Scholar
  187. Z. B. Han, H. Y. Chen, J. W. Fan, J. Y. Wu, H. M. Tang, and Z. H. Peng, “Up-regulation of microRNA-155 promotes cancer cell invasion and predicts poor survival of hepatocellular carcinoma following liver transplantation,” Journal of Cancer Research and Clinical Oncology, vol. 138, pp. 153–161, 2012. View at Google Scholar
  188. A. Karakatsanis, I. Papaconstantinou, M. Gazouli, A. Lyberopoulou, G. Polymeneas, and D. Voros, “Expression of microRNAs, miR-21, miR-31, miR-122, miR-145, miR-146a, miR-200c, miR-221, miR-222, and miR-223 in patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma and its prognostic significance,” Molecular Carcinogenesis, 2011. View at Publisher · View at Google Scholar
  189. A. Budhu, H. L. Jia, M. Forgues et al., “Identification of metastasis-related microRNAs in hepatocellular carcinoma,” Hepatology, vol. 47, no. 3, pp. 897–907, 2008. View at Publisher · View at Google Scholar · View at Scopus
  190. J. Jiang, Y. Gusev, I. Aderca et al., “Association of microRNA expression in hepatocellular carcinomas with hepatitis infection, cirrhosis, and patient survival,” Clinical Cancer Research, vol. 14, no. 2, pp. 419–427, 2008. View at Publisher · View at Google Scholar · View at Scopus
  191. 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
  192. Y. Yamamoto, N. Kosaka, M. Tanaka et al., “MicroRNA-500 as a potential diagnostic marker for hepatocellular carcinoma,” Biomarkers, vol. 14, no. 7, pp. 529–538, 2009. View at Publisher · View at Google Scholar · View at Scopus
  193. M. Shigoka, A. Tsuchida, T. Matsudo et al., “Deregulation of miR-92a expression is implicated in hepatocellular carcinoma development,” Pathology International, vol. 60, no. 5, pp. 351–357, 2010. View at Publisher · View at Google Scholar · View at Scopus
  194. L. M. Li, Z. B. Hu, Z. X. Zhou et al., “Serum microRNA profiles serve as novel biomarkers for HBV infection and diagnosis of HBV-positive hepatocarcinoma,” Cancer Research, vol. 70, no. 23, pp. 9798–9807, 2010. View at Publisher · View at Google Scholar · View at Scopus
  195. J. K. Park, T. Kogure, G. J. Nuovo et al., “miR-221 silencing blocks hepatocellular carcinoma and promotes survival,” Cancer Research, vol. 71, pp. 7608–7616, 2011. View at Google Scholar
  196. E. Callegari, B. K. Elamin, F. Giannone et al., “Liver tumorigenicity promoted by microRNA-221 in a mouse transgenic model,” Hepatology, vol. 56, pp. 1025–1033, 2012. View at Google Scholar
  197. S. Bai, M. W. Nasser, B. Wang et al., “MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib,” Journal of Biological Chemistry, vol. 284, no. 46, pp. 32015–32027, 2009. View at Publisher · View at Google Scholar · View at Scopus