Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2014, Article ID 376326, 14 pages
http://dx.doi.org/10.1155/2014/376326
Review Article

Role of miRNA Let-7 and Its Major Targets in Prostate Cancer

1Small Animal Clinic, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
2Institute of Biophysics, University Hannover, 30419 Hannover, Germany
3Division of Medicine, Department of Haematology/Oncology, University of Rostock, 18057 Rostock, Germany

Received 16 April 2014; Revised 11 August 2014; Accepted 18 August 2014; Published 3 September 2014

Academic Editor: Andreas Doll

Copyright © 2014 Siegfried Wagner 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. L. Kopper and J. Tímár, “Genomics of prostate cancer: is there anything to “translate”?” Pathology & Oncology Research, vol. 11, no. 4, pp. 197–203, 2005. View at Publisher · View at Google Scholar · View at Scopus
  2. L. Bubendorf, A. Schöpfer, U. Wagner et al., “Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients,” Human Pathology, vol. 31, no. 5, pp. 578–583, 2000. View at Publisher · View at Google Scholar · View at Scopus
  3. R. T. Divrik, L. Türkeri, A. F. Şahin et al., “Prediction of response to androgen deprivation therapy and castration resistance in primary metastatic prostate cancer,” Urologia Internationalis, vol. 88, no. 1, pp. 25–33, 2012. View at Publisher · View at Google Scholar · View at Scopus
  4. 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
  5. R. T. Greenlee, T. Murray, S. Bolden, and P. A. Wingo, “Cancer statistics, 2000,” CA: A Cancer Journal for Clinicians, vol. 50, no. 1, pp. 7–33, 2000. View at Publisher · View at Google Scholar · View at Scopus
  6. G. L. Andriole, E. D. Crawford, R. L. Grubb III et al., “Mortality results from a randomized prostate-cancer screening trial,” New England Journal of Medicine, vol. 360, no. 13, pp. 1310–1319, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. F. H. Schröder, J. Hugosson, M. J. Roobol et al., “Screening and prostate-cancer mortality in a randomized european study,” The New England Journal of Medicine, vol. 360, no. 13, pp. 1320–1328, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. E. Basch, T. K. Oliver, A. Vickers et al., “Screening for prostate cancer with prostate-specific antigen testing: american society of clinical oncology provisional clinical opinion,” Journal of Clinical Oncology, vol. 30, no. 24, pp. 3020–3025, 2012. View at Publisher · View at Google Scholar · View at Scopus
  9. H. Ramberg, A. Alshbib, V. Berge, A. Svindland, and K. A. Taskén, “Regulation of PBX3 expression by androgen and Let-7d in prostate cancer,” Molecular Cancer, vol. 10, article 50, 2011. View at Publisher · View at Google Scholar · View at Scopus
  10. N. Nadiminty, R. Tummala, W. Lou et al., “MicroRNA let-7c is downregulated in prostate cancer and suppresses prostate cancer growth,” PLoS ONE, vol. 7, no. 3, Article ID e32832, 2012. View at Publisher · View at Google Scholar · View at Scopus
  11. Q. Dong, P. Meng, T. Wang et al., “MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2,” PLoS ONE, vol. 5, no. 4, Article ID e10147, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. N. Nadiminty, R. Tummala, W. Lou et al., “MicroRNA let-7c suppresses androgen receptor expression and activity via regulation of myc expression in prostate cancer cells,” Journal of Biological Chemistry, vol. 287, no. 2, pp. 1527–1537, 2012. View at Publisher · View at Google Scholar · View at Scopus
  13. 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
  14. Y. Lee, C. Ahn, J. Han et al., “The nuclear RNase III Drosha initiates microRNA processing,” Nature, vol. 425, no. 6956, pp. 415–419, 2003. View at Publisher · View at Google Scholar · View at Scopus
  15. G. Meister, “Argonaute proteins: functional insights and emerging roles,” Nature Reviews Genetics, vol. 14, no. 7, pp. 447–459, 2013. View at Publisher · View at Google Scholar · View at Scopus
  16. V. Mondol and A. E. Pasquinelli, “Let's make it happen: the role of let-7 microRNA in development,” Current Topics in Developmental Biology, vol. 99, pp. 1–30, 2012. View at Publisher · View at Google Scholar · View at Scopus
  17. 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
  18. H.-W. Hwang, E. A. Wentzel, and J. T. Mendell, “A hexanucleotide element directs microRNA nuclear import,” Science, vol. 315, no. 5808, pp. 97–100, 2007. View at Publisher · View at Google Scholar · View at Scopus
  19. R. F. Place, L.-C. Li, D. Pookot, E. J. Noonan, and R. Dahiya, “MicroRNA-373 induces expression of genes with complementary promoter sequences,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 5, pp. 1608–1613, 2008. View at Publisher · View at Google Scholar · View at Scopus
  20. 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
  21. P.-S. Chen, J.-L. Su, S.-T. Cha et al., “miR-107 promotes tumor progression by targeting the let-7 microRNA in mice and humans,” The Journal of Clinical Investigation, vol. 121, no. 9, pp. 3442–3455, 2011. View at Publisher · View at Google Scholar · View at Scopus
  22. J. Winter, S. Jung, S. Keller, R. I. Gregory, and S. Diederichs, “Many roads to maturity: microRNA biogenesis pathways and their regulation,” Nature Cell Biology, vol. 11, no. 3, pp. 228–234, 2009. View at Publisher · View at Google Scholar · View at Scopus
  23. B. N. Davis and A. Hata, “Regulation of MicroRNA Biogenesis: a miRiad of mechanisms,” Cell Communication and Signaling, vol. 7, article 18, 2009. View at Publisher · View at Google Scholar · View at Scopus
  24. 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
  25. S. Roush and F. J. Slack, “The let-7 family of microRNAs,” Trends in Cell Biology, vol. 18, no. 10, pp. 505–516, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. B. Boyerinas, S.-M. Park, A. Hau, A. E. Murmann, and M. E. Peter, “The role of let-7 in cell differentiation and cancer,” Endocrine-Related Cancer, vol. 17, no. 1, pp. F19–F36, 2010. View at Publisher · View at Google Scholar · View at Scopus
  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. M. H. Bao, X. Feng, Y. W. Zhang, X. Y. Lou, Y. Cheng, and H. H. Zhou, “Let-7 in cardiovascular diseases, heart development and cardiovascular differentiation from stem cells,” International Journal of Molecular Sciences, vol. 14, no. 11, pp. 23086–23102, 2013. View at Google Scholar
  29. W. Hou, Q. Tian, N. M. Steuerwald, L. W. Schrum, and H. L. Bonkovsky, “The let-7 microRNA enhances heme oxygenase-1 by suppressing Bach1 and attenuates oxidant injury in human hepatocytes,” Biochimica et Biophysica Acta: Gene Regulatory Mechanisms, vol. 1819, no. 11-12, pp. 1113–1122, 2012. View at Publisher · View at Google Scholar · View at Scopus
  30. S. Polikepahad, J. M. Knight, A. O. Naghavi et al., “Proinflammatory role for let-7 microRNAS in experimental asthma,” Journal of Biological Chemistry, vol. 285, no. 39, pp. 30139–30149, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. D. Iliopoulos, H. A. Hirsch, and K. Struhl, “An epigenetic switch involving NF-κB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation,” Cell, vol. 139, no. 4, pp. 693–706, 2009. View at Publisher · View at Google Scholar · View at Scopus
  32. C. D. Johnson, A. Esquela-Kerscher, G. Stefani et al., “The let-7 microRNA represses cell proliferation pathways in human cells,” Cancer Research, vol. 67, no. 16, pp. 7713–7722, 2007. View at Publisher · View at Google Scholar · View at Scopus
  33. 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
  34. F. Meng, R. Henson, H. Wehbe-Janek, H. Smith, Y. Ueno, and T. Patel, “The microRNA let-7a modulates interleukin-6-dependent STAT-3 survival signaling in malignant human cholangiocytes,” The Journal of Biological Chemistry, vol. 282, no. 11, pp. 8256–8264, 2007. View at Publisher · View at Google Scholar · View at Scopus
  35. 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
  36. C. Liu, K. Kelnar, A. V. Vlassov, D. Brown, J. Wang, and D. G. Tang, “Distinct microRNA expression profiles in prostate cancer stem/progenitor cells and tumor-suppressive functions of let-7,” Cancer Research, vol. 72, no. 13, pp. 3393–3405, 2012. View at Publisher · View at Google Scholar · View at Scopus
  37. T. Reya, S. J. Morrison, M. F. Clarke, and I. L. Weissman, “Stem cells, cancer, and cancer stem cells,” Nature, vol. 414, no. 6859, pp. 105–111, 2001. View at Publisher · View at Google Scholar · View at Scopus
  38. L. M. Coussens and Z. Werb, “Inflammation and cancer,” Nature, vol. 420, no. 6917, pp. 860–867, 2002. View at Publisher · View at Google Scholar · View at Scopus
  39. D. Kong, S. Banerjee, A. Ahmad et al., “Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells,” PLoS ONE, vol. 5, no. 8, Article ID e12445, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. S. N. Shah, L. Cope, W. Poh et al., “HMGA1: a master regulator of tumor progression in triple-negative breast cancer cells,” PLoS ONE, vol. 8, no. 5, Article ID e63419, 2013. View at Publisher · View at Google Scholar · View at Scopus
  41. C. Zhu, J. Li, G. Cheng et al., “MiR-154 inhibits EMT by targeting HMGA2 in prostate cancer cells,” Molecular and Cellular Biochemistry, vol. 379, no. 1-2, pp. 69–75, 2013. View at Publisher · View at Google Scholar · View at Scopus
  42. 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
  43. K. Patel, A. Kollory, A. Takashima, S. Sarkar, D. V. Faller, and S. K. Ghosh, “MicroRNA let-7 downregulates STAT3 phosphorylation in pancreatic cancer cells by increasing SOCS3 expression,” Cancer Letters, vol. 347, no. 1, pp. 54–64, 2014. View at Publisher · View at Google Scholar
  44. M. M. Rahman, Z. R. Qian, E. L. Wang et al., “Frequent overexpression of HMGA1 and 2 in gastroenteropancreatic neuroendocrine tumours and its relationship to let-7 downregulation,” British Journal of Cancer, vol. 100, no. 3, pp. 501–510, 2009. View at Publisher · View at Google Scholar · View at Scopus
  45. S. Watanabe, Y. Ueda, S.-I. Akaboshi, Y. Hino, Y. Sekita, and M. Nakao, “HMGA2 maintains oncogenic RAS-induced epithelial-mesenchymal transition in human pancreatic cancer cells,” The American Journal of Pathology, vol. 174, no. 3, pp. 854–868, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. E. Piskounova, C. Polytarchou, J. E. Thornton et al., “Lin28A and Lin28B inhibit let-7 MicroRNA biogenesis by distinct mechanisms,” Cell, vol. 147, no. 5, pp. 1066–1079, 2011. View at Publisher · View at Google Scholar · View at Scopus
  47. 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
  48. L. J. Wood, M. Mukherjee, C. E. Dolde et al., “HMG-I/Y, a new c-Myc target gene and potential oncogene,” Molecular and Cellular Biology, vol. 20, no. 15, pp. 5490–5502, 2000. View at Publisher · View at Google Scholar · View at Scopus
  49. S. Y. Sung, C. H. Liao, H. P. Wu et al., “Loss of let-7 microRNA upregulates IL-6 in bone marrow-derived mesenchymal stem cells triggering a reactive stromal response to prostate cancer,” PloS ONE, vol. 8, no. 8, Article ID e71637, 2013. View at Google Scholar
  50. S. N. Shah, C. Kerr, L. Cope et al., “HMGA1 reprograms somatic cells into pluripotent stem cells by inducing stem cell transcriptional networks,” PLoS ONE, vol. 7, no. 11, Article ID e48533, 2012. View at Publisher · View at Google Scholar · View at Scopus
  51. G. M. Pierantoni, C. Rinaldo, M. Mottolese et al., “High-mobility group A1 inhibits p53 by cytoplasmic relocalization of its proapoptotic activator HIPK2,” The Journal of Clinical Investigation, vol. 117, no. 3, pp. 693–702, 2007. View at Publisher · View at Google Scholar · View at Scopus
  52. T. Ueda and M. Yoshida, “HMGB proteins and transcriptional regulation,” Biochimica et Biophysica Acta—Gene Regulatory Mechanisms, vol. 1799, no. 1-2, pp. 114–118, 2010. View at Publisher · View at Google Scholar · View at Scopus
  53. S. Lyu, Q. Yu, G. Ying et al., “Androgen receptor decreases CMYC and KRAS expression by upregulating let-7a expression in ER-, PR-, AR+ breast cancer,” International Journal of Oncology, vol. 44, no. 1, pp. 229–237, 2013. View at Google Scholar
  54. M. Bustin, “Revised nomenclature for high mobility group (HMG) chromosomal proteins,” Trends in Biochemical Sciences, vol. 26, no. 3, pp. 152–153, 2001. View at Google Scholar · View at Scopus
  55. K. R. Diener, N. Al-Dasooqi, E. L. Lousberg, and J. D. Hayball, “The multifunctional alarmin HMGB1 with roles in the pathophysiology of sepsis and cancer,” Immunology and Cell Biology, vol. 91, pp. 443–450, 2013. View at Publisher · View at Google Scholar · View at Scopus
  56. R. Reeves, “Nuclear functions of the HMG proteins,” Biochimica et Biophysica Acta—Gene Regulatory Mechanisms, vol. 1799, no. 1-2, pp. 3–14, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. M. Fedele and A. Fusco, “HMGA and cancer,” Biochimica et Biophysica Acta: Gene Regulatory Mechanisms, vol. 1799, no. 1-2, pp. 48–54, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. Y. Tamimi, H. G. van der Poel, M.-M. Denyn et al., “Increased expression of high mobility group protein I(Y) in high grade prostatic cancer determined by in situ hybridization,” Cancer Research, vol. 53, no. 22, pp. 5512–5516, 1993. View at Google Scholar · View at Scopus
  59. J.-J. Wei, X. Wu, Y. Peng et al., “Regulation of HMGA1 expression by MicroRNA-296 affects prostate cancer growth and invasion,” Clinical Cancer Research, vol. 17, no. 6, pp. 1297–1305, 2011. View at Publisher · View at Google Scholar · View at Scopus
  60. J. Hillion, L. J. Wood, M. Mukherjee et al., “Upregulation of MMP-2 by HMGA1 promotes transformation in undifferentiated, large-cell lung cancer,” Molecular Cancer Research, vol. 7, no. 11, pp. 1803–1812, 2009. View at Publisher · View at Google Scholar · View at Scopus
  61. R. Reeves, D. D. Edberg, and Y. Li, “Architectural transcription factor HMGI(Y) promotes tumor progression and mesenchymal transition of human epithelial cells,” Molecular and Cellular Biology, vol. 21, no. 2, pp. 575–594, 2001. View at Publisher · View at Google Scholar · View at Scopus
  62. N. Takaha, A. L. Hawkins, C. A. Griffin, W. B. Isaacs, and D. S. Coffey, “High mobility group protein I(Y): a candidate architectural protein for chromosomal rearrangements in prostate cancer cells,” Cancer Research, vol. 62, no. 3, pp. 647–651, 2002. View at Google Scholar · View at Scopus
  63. N. Takaha, L. M. S. Resar, D. Vindivich, and D. S. Coffey, “High mobility group protein HMGI(Y) enhances tumor cell growth, invasion, and matrix metalloproteinase-2 expression in prostate cancer cells,” The Prostate, vol. 60, no. 2, pp. 160–167, 2004. View at Publisher · View at Google Scholar · View at Scopus
  64. A. Cano, M. A. Pérez-Moreno, I. Rodrigo et al., “The transcription factor Snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression,” Nature Cell Biology, vol. 2, no. 2, pp. 76–83, 2000. View at Publisher · View at Google Scholar · View at Scopus
  65. J. Pérez-Losada, M. Sánchez-Martin, A. Rodríguez-García et al., “Zinc-finger transcription factor slug contributes to the function of the stem cell factor c-kit signaling pathway,” Blood, vol. 100, no. 4, pp. 1274–1286, 2002. View at Google Scholar · View at Scopus
  66. I. De Martino, R. Visone, M. Fedele et al., “Regulation of microRNA expression by HMGA1 proteins,” Oncogene, vol. 28, no. 11, pp. 1432–1442, 2009. View at Publisher · View at Google Scholar · View at Scopus
  67. J. Hillion, S. Dhara, T. F. Sumter et al., “The high-mobility group A1a/signal transducer and activator of transcription-3 axis: an achilles heel for hematopoietic malignancies?” Cancer Research, vol. 68, no. 24, pp. 10121–10127, 2008. View at Publisher · View at Google Scholar · View at Scopus
  68. O. A. Timofeeva, N. I. Tarasova, X. Zhang et al., “STAT3 suppresses transcription of proapoptotic genes in cancer cells with the involvement of its N-terminal domain,” Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 4, pp. 1267–1272, 2013. View at Publisher · View at Google Scholar · View at Scopus
  69. D. Iliopoulos, S. A. Jaeger, H. A. Hirsch, M. L. Bulyk, and K. Struhl, “STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer,” Molecular Cell, vol. 39, no. 4, pp. 493–506, 2010. View at Publisher · View at Google Scholar · View at Scopus
  70. J. Ma, H. Sawai, N. Ochi et al., “PTEN regulate angiogenesis through PI3K/Akt/VEGF signaling pathway in human pancreatic cancer cells,” Molecular and Cellular Biochemistry, vol. 331, no. 1-2, pp. 161–171, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. R. Sgarra, S. Zammitti, A. Lo Sardo et al., “HMGA molecular network: from transcriptional regulation to chromatin remodeling,” Biochimica et Biophysica Acta—Gene Regulatory Mechanisms, vol. 1799, no. 1-2, pp. 37–47, 2010. View at Publisher · View at Google Scholar · View at Scopus
  72. G. Mu, H. Liu, F. Zhou et al., “Correlation of overexpression of HMGA1 and HMGA2 with poor tumor differentiation, invasion, and proliferation associated with let-7 down-regulation in retinoblastomas,” Human Pathology, vol. 41, no. 4, pp. 493–502, 2010. View at Publisher · View at Google Scholar · View at Scopus
  73. D. Palmieri, D. D'Angelo, T. Valentino et al., “Downregulation of HMGA-targeting microRNAs has a critical role in human pituitary tumorigenesis,” Oncogene, vol. 31, no. 34, pp. 3857–3865, 2012. View at Publisher · View at Google Scholar · View at Scopus
  74. M. Schubert, M. Spahn, S. Kneitz et al., “Distinct microRNA expression profile in prostate cancer patients with early clinical failure and the impact of let-7 as prognostic marker in high-risk prostate cancer,” PLoS ONE, vol. 8, no. 6, Article ID e65064, 2013. View at Publisher · View at Google Scholar · View at Scopus
  75. B. Meyer, S. Loeschke, A. Schultze et al., “HMGA2 overexpression in non-small cell lung cancer,” Molecular Carcinogenesis, vol. 46, no. 7, pp. 503–511, 2007. View at Publisher · View at Google Scholar · View at Scopus
  76. P. Rogalla, K. Drechsler, B. Kazmierczak, V. Rippe, U. Bonk, and J. Bullerdiek, “Expression of HMGI-C, a member of the high mobility group protein family, in a subset of breast cancers: relationship to histologic grade,” Molecular Carcinogenesis, vol. 19, no. 3, pp. 153–156, 1997. View at Google Scholar
  77. S. Winkler, H. M. Escobar, B. Meyer et al., “HMGA2 expression in a canine model of prostate cancer,” Cancer Genetics and Cytogenetics, vol. 177, no. 2, pp. 98–102, 2007. View at Publisher · View at Google Scholar · View at Scopus
  78. M. S. Kumar, E. Armenteros-Monterroso, P. East et al., “HMGA2 functions as a competing endogenous RNA to promote lung cancer progression,” Nature, vol. 505, no. 7482, pp. 212–217, 2014. View at Google Scholar
  79. M. T. Berlingieri, G. Manfioletti, M. Santoro et al., “Inhibition of HMGI-C protein synthesis suppresses retrovirally induced neoplastic transformation of rat thyroid cells,” Molecular and Cellular Biology, vol. 15, no. 3, pp. 1545–1553, 1995. View at Google Scholar · View at Scopus
  80. J.-M. Berner, L. A. Meza-Zepeda, P. F. J. Kools et al., “HMGIC, the gene for an architectural transcription factor, is amplified and rearranged in a subset of human sarcomas,” Oncogene, vol. 14, no. 24, pp. 2935–2941, 1997. View at Publisher · View at Google Scholar · View at Scopus
  81. F. di Cello, J. Hillion, A. Hristov et al., “HMGA2 participates in transformation in human lung cancer,” Molecular Cancer Research, vol. 6, no. 5, pp. 743–750, 2008. View at Publisher · View at Google Scholar · View at Scopus
  82. M. Fedele, S. Battista, G. Manfioletti, C. M. Croce, V. Giancotti, and A. Fusco, “Role of the high mobility group A proteins in human lipomas,” Carcinogenesis, vol. 22, no. 10, pp. 1583–1591, 2001. View at Publisher · View at Google Scholar · View at Scopus
  83. S. Müller, P. Scaffidi, B. Degryse et al., “The double life of HMGB1 chromatin protein: architectural factor and extracellular signal,” The EMBO Journal, vol. 20, no. 16, pp. 4337–4340, 2001. View at Publisher · View at Google Scholar · View at Scopus
  84. E. Pikarsky, R. M. Porat, I. Stein et al., “NF-κB functions as a tumour promoter in inflammation-associated cancer,” Nature, vol. 431, no. 7007, pp. 461–466, 2004. View at Publisher · View at Google Scholar · View at Scopus
  85. J. R. van Beijnum, W. A. Buurman, and A. W. Griffioen, “Convergence and amplification of toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signaling pathways via high mobility group B1 (HMGB1),” Angiogenesis, vol. 11, no. 1, pp. 91–99, 2008. View at Publisher · View at Google Scholar · View at Scopus
  86. J. S. Park, D. Svetkauskaite, Q. He et al., “Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein,” The Journal of Biological Chemistry, vol. 279, no. 9, pp. 7370–7377, 2004. View at Publisher · View at Google Scholar · View at Scopus
  87. O. Hori, J. Brett, T. Slattery et al., “The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of RAGE and amphoterin in the developing nervous system,” The Journal of Biological Chemistry, vol. 270, no. 43, pp. 25752–25761, 1995. View at Publisher · View at Google Scholar · View at Scopus
  88. X. M. Chen, P. L. Splinter, S. P. O'Hara, and N. F. LaRusso, “A cellular micro-RNA, let-7i, regulates Toll-like receptor 4 expression and contributes to cholangiocyte immune responses against Cryptosporidium parvum infection,” The Journal of Biological Chemistry, vol. 282, no. 39, pp. 28929–28938, 2007. View at Google Scholar
  89. G. Li, J. Xu, and Z. Li, “Receptor for advanced glycation end products inhibits proliferation in osteoblast through suppression of Wnt, PI3K and ERK signaling,” Biochemical and Biophysical Research Communications, vol. 423, no. 4, pp. 684–689, 2012. View at Publisher · View at Google Scholar · View at Scopus
  90. J. E. Hutti, A. D. Pfefferle, S. C. Russell, M. Sircar, C. M. Perou, and A. S. Baldwin, “Oncogenic PI3K mutations lead to NF-κB-dependent cytokine expression following growth factor deprivation,” Cancer Research, vol. 72, no. 13, pp. 3260–3269, 2012. View at Publisher · View at Google Scholar · View at Scopus
  91. M. Yu, H. Wang, A. Ding et al., “HMGB1 signals through toll-like receptor (TLR) 4 and TLR2,” Shock, vol. 26, no. 2, pp. 174–179, 2006. View at Publisher · View at Google Scholar · View at Scopus
  92. J. Li and A. M. Schmidt, “Characterization and functional analysis of the promoter of RAGE, the receptor for advanced glycation end products,” The Journal of Biological Chemistry, vol. 272, no. 26, pp. 16498–16506, 1997. View at Publisher · View at Google Scholar · View at Scopus
  93. A. Taguchi, D. C. Blood, G. Del Toro et al., “Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases,” Nature, vol. 405, no. 6784, pp. 354–360, 2000. View at Publisher · View at Google Scholar · View at Scopus
  94. D. Tang, R. Kang, H. J. Zeh III, and M. T. Lotze, “High-mobility group box 1 and cancer,” Biochimica et Biophysica Acta—Gene Regulatory Mechanisms, vol. 1799, no. 1-2, pp. 131–140, 2010. View at Publisher · View at Google Scholar · View at Scopus
  95. H. Kuniyasu, Y. Chihara, H. Kondo, H. Ohmori, and R. Ukai, “Amphoterin induction in prostatic stromal cells by androgen deprivation is associated with metastatic prostate cancer.,” Oncology Reports, vol. 10, no. 6, pp. 1863–1868, 2003. View at Google Scholar · View at Scopus
  96. M. Gnanasekar, R. Kalyanasundaram, G. Zheng, A. Chen, M. C. Bosland, and A. Kajdacsy-Balla, “HMGB1: a promising therapeutic target for prostate cancer,” Prostate Cancer, vol. 2013, Article ID 157103, 8 pages, 2013. View at Publisher · View at Google Scholar
  97. V. Boonyaratanakornkit, V. Melvin, P. Prendergast et al., “High-mobility group chromatin proteins 1 and 2 functionally interact with steroid hormone receptors to enhance their DNA binding in vitro and transcriptional activity in mammalian cells,” Molecular and Cellular Biology, vol. 18, no. 8, pp. 4471–4487, 1998. View at Google Scholar
  98. J. P. Rowell, K. L. Simpson, K. Stott, M. Watson, and J. O. Thomas, “HMGB1-facilitated p53 DNA binding occurs via HMG-Box/p53 transactivation domain interaction, regulated by the acidic tail,” Structure, vol. 20, no. 12, pp. 2014–2024, 2012. View at Publisher · View at Google Scholar · View at Scopus
  99. H. Uramoto, H. Izumi, G. Nagatani et al., “Physical interaction of tumour suppressor p53/p73 with CCAAT-binding transcription factor 2 (CTF2) and differential regulation of human high-mobility group 1 (HMG1) gene expression,” The Biochemical Journal, vol. 371, no. 2, pp. 301–310, 2003. View at Publisher · View at Google Scholar · View at Scopus
  100. A. D. Saleh, J. E. Savage, L. Cao et al., “Cellular stress induced alterations in microrna let-7a and let-7b expression are dependent on p53,” PLoS ONE, vol. 6, no. 10, Article ID e24429, 2011. View at Publisher · View at Google Scholar · View at Scopus
  101. M. Malumbres and M. Barbacid, “Cell cycle, CDKs and cancer: a changing paradigm,” Nature Reviews Cancer, vol. 9, no. 3, pp. 153–166, 2009. View at Publisher · View at Google Scholar · View at Scopus
  102. Y. Takano, Y. Kato, P. J. Van Diest, M. Masuda, H. Mitomi, and I. Okayasu, “Cyclin D2 overexpression and lack of p27 correlate positively and cyclin E inversely with a poor prognosis in gastric cancer cases,” The American Journal of Pathology, vol. 156, no. 2, pp. 585–594, 2000. View at Publisher · View at Google Scholar · View at Scopus
  103. A. Mermelshtein, A. Gerson, S. Walfisch et al., “Expression of D-type cyclins in colon cancer and in cell lines from colon carcinomas,” British Journal of Cancer, vol. 93, no. 3, pp. 338–345, 2005. View at Publisher · View at Google Scholar · View at Scopus
  104. T. Igawa, Y. Sato, K. Takata et al., “Cyclin D2 is overexpressed in proliferation centers of chronic lymphocytic leukemia/small lymphocytic lymphoma,” Cancer Science, vol. 102, no. 11, pp. 2103–2107, 2011. View at Publisher · View at Google Scholar · View at Scopus
  105. C. Zhu, P. Shao, M. Bao et al., “miR-154 inhibits prostate cancer cell proliferation by targeting CCND2,” Urologic Oncology: Seminars and Original Investigations, vol. 32, no. 1, pp. 31.e9–31.e16, 2014. View at Publisher · View at Google Scholar · View at Scopus
  106. J. Klaewsongkram, Y. Yang, S. Golech, J. Katz, K. H. Kaestner, and N.-P. Weng, “Krüppel-like factor 4 regulates B cell number and activation-induced B cell proliferation,” Journal of Immunology, vol. 179, no. 7, pp. 4679–4684, 2007. View at Publisher · View at Google Scholar · View at Scopus
  107. C. Bouchard, O. Dittrich, A. Kiermaier et al., “Regulation of cyclin D2 gene expression by the Myc/Max/Mad network: Myc-dependent TRRAP recruitment and histone acetylation at the cyclin D2 promoter,” Genes & Development, vol. 15, no. 16, pp. 2042–2047, 2001. View at Publisher · View at Google Scholar · View at Scopus
  108. C. E. Nesbit, J. M. Tersak, and E. V. Prochownik, “MYC oncogenes and human neoplastic disease,” Oncogene, vol. 18, no. 19, pp. 3004–3016, 1999. View at Publisher · View at Google Scholar · View at Scopus
  109. C. V. Dang, “MYC, metabolism, cell growth, and tumorigenesis,” Cold Spring Harbor Perspectives in Medicine, vol. 3, no. 8, 2013. View at Publisher · View at Google Scholar · View at Scopus
  110. B. Nagy, A. Szendroi, and I. Romics, “Overexpression of CD24, c-myc and phospholipase 2A in prostate cancer tissue samples obtained by needle biopsy,” Pathology and Oncology Research, vol. 15, no. 2, pp. 279–283, 2009. View at Publisher · View at Google Scholar · View at Scopus
  111. R. Buttyan, I. S. Sawczuk, M. C. Benson, J. D. Siegal, and C. Olsson, “Enhanced expression of the c-myc protooncogene in high-grade human prostate cancers,” The Prostate, vol. 11, no. 4, pp. 327–337, 1987. View at Publisher · View at Google Scholar · View at Scopus
  112. J. Gil, P. Kerai, M. Lleonart et al., “Immortalization of primary human prostate epithelial cells by c-Myc,” Cancer Research, vol. 65, no. 6, pp. 2179–2185, 2005. View at Publisher · View at Google Scholar · View at Scopus
  113. S. R. Hann, “Role of post-translational modifications in regulating c-Myc proteolysis, transcriptional activity and biological function,” Seminars in Cancer Biology, vol. 16, no. 4, pp. 288–302, 2006. View at Publisher · View at Google Scholar · View at Scopus
  114. H. K. Hyeon, Y. Kuwano, S. Srikantan, K. L. Eun, J. L. Martindale, and M. Gorospe, “HuR recruits let-7/RISC to repress c-Myc expression,” Genes and Development, vol. 23, no. 15, pp. 1743–1748, 2009. View at Publisher · View at Google Scholar · View at Scopus
  115. 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
  116. D. Gioeli, J. W. Mandell, G. R. Petroni, H. F. Frierson Jr., and M. J. Weber, “Activation of mitogen-activated protein kinase associated with prostate cancer progression,” Cancer research, vol. 59, no. 2, pp. 279–284, 1999. View at Google Scholar
  117. F. Marampon, C. Ciccarelli, and B. M. Zani, “Down-regulation of c-Myc following MEK/ERK inhibition halts the expression of malignant phenotype in rhabdomyosarcoma and in non muscle-derived human tumors,” Molecular Cancer, vol. 5, article 31, 2006. View at Publisher · View at Google Scholar · View at Scopus
  118. C. Bradham and D. R. McClay, “p38 MAPK in development and cancer,” Cell Cycle, vol. 5, no. 8, pp. 824–828, 2006. View at Google Scholar
  119. T.-C. Chang, L. R. Zeitels, H.-W. Hwang et al., “Lin-28B transactivation is necessary for Myc-mediated let-7 repression and proliferation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 9, pp. 3384–3389, 2009. View at Publisher · View at Google Scholar · View at Scopus
  120. K. S. Sfanos and A. M. de Marzo, “Prostate cancer and inflammation: the evidence,” Histopathology, vol. 60, no. 1, pp. 199–215, 2012. View at Publisher · View at Google Scholar · View at Scopus
  121. T. Hirano, K. Yasukawa, H. Harada et al., “Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin,” Nature, vol. 324, no. 6092, pp. 73–76, 1986. View at Publisher · View at Google Scholar · View at Scopus
  122. D. P. Nguyen, J. Li, and A. K. Tewari, “Inflammation and prostate cancer: the role of interleukin 6 (IL-6),” BJU International, vol. 113, no. 6, pp. 986–992, 2014. View at Google Scholar
  123. M. Okamoto, C. Lee, and R. Oyasu, “Interleukin-6 as a paracrine and autocrine growth factor in human prostatic carcinoma cells in vitro,” Cancer Research, vol. 57, no. 1, pp. 141–146, 1997. View at Google Scholar · View at Scopus
  124. B. Wegiel, A. Bjartell, Z. Culig, and J. L. Persson, “Interleukin-6 activates PI3K/Akt pathway and regulates cyclin A1 to promote prostate cancer cell survival,” International Journal of Cancer, vol. 122, no. 7, pp. 1521–1529, 2008. View at Publisher · View at Google Scholar · View at Scopus
  125. P. Sivashanmugam, L. Tang, and Y. Daaka, “Interleukin 6 mediates the lysophosphatidic acid-regulated cross-talk between stromal and epithelial prostate cancer cells,” Journal of Biological Chemistry, vol. 279, no. 20, pp. 21154–21159, 2004. View at Publisher · View at Google Scholar · View at Scopus
  126. D. Giri, M. Ozen, and M. Ittmann, “Interleukin-6 is an autocrine growth factor in human prostate cancer,” The American Journal of Pathology, vol. 159, no. 6, pp. 2159–2165, 2001. View at Publisher · View at Google Scholar · View at Scopus
  127. V. Michalaki, K. Syrigos, P. Charles, and J. Waxman, “Serum levels of IL-6 and TNF-α correlate with clinicopathological features and patient survival in patients with prostate cancer,” British Journal of Cancer, vol. 90, no. 12, pp. 2312–2316, 2004. View at Google Scholar · View at Scopus
  128. R. J. Simpson, A. Hammacher, D. K. Smith, J. M. Matthews, and L. D. Ward, “Interleukin-6: structure-function relationships,” Protein Science, vol. 6, no. 5, pp. 929–955, 1997. View at Publisher · View at Google Scholar · View at Scopus
  129. K. Yamaoka, P. Saharinen, M. Pesu, V. E. T. Holt III, O. Silvennoinen, and J. J. O'Shea, “The Janus kinases (Jaks),” Genome Biology, vol. 5, no. 12, article 253, 2004. View at Publisher · View at Google Scholar · View at Scopus
  130. X. Wang, P. Lupardus, S. L. LaPorte, and K. C. Garcia, “Structural biology of shared cytokine receptors,” Annual Review of Immunology, vol. 27, pp. 29–60, 2009. View at Publisher · View at Google Scholar · View at Scopus
  131. J. N. Ihle, “The stat family in cytokine signaling,” Current Opinion in Cell Biology, vol. 13, no. 2, pp. 211–217, 2001. View at Publisher · View at Google Scholar · View at Scopus
  132. J. Scheller, A. Chalaris, D. Schmidt-Arras, and S. Rose-John, “The pro- and anti-inflammatory properties of the cytokine interleukin-6,” Biochimica et Biophysica Acta: Molecular Cell Research, vol. 1813, no. 5, pp. 878–888, 2011. View at Publisher · View at Google Scholar · View at Scopus
  133. A. Fahmi, N. Smart, A. Punn, R. Jabr, M. Marber, and R. Heads, “P42/p44-MAPK and PI3K are sufficient for IL-6 family cytokines/gp130 to signal to hypertrophy and survival in cardiomyocytes in the absence of JAK/STAT activation,” Cellular Signalling, vol. 25, no. 4, pp. 898–909, 2013. View at Publisher · View at Google Scholar · View at Scopus
  134. T. Ueda, N. Bruchovsky, and M. D. Sadar, “Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways,” The Journal of Biological Chemistry, vol. 277, no. 9, pp. 7076–7085, 2002. View at Publisher · View at Google Scholar · View at Scopus
  135. K. Malinowska, H. Neuwirt, I. T. Cavarretta et al., “Interleukin-6 stimulation of growth of prostate cancer in vitro and in vivo through activation of the androgen receptor,” Endocrine-Related Cancer, vol. 16, no. 1, pp. 155–169, 2009. View at Publisher · View at Google Scholar · View at Scopus
  136. L. Yang, L. Wang, H.-K. Lin et al., “Interleukin-6 differentially regulates androgen receptor transactivation via PI3K-Akt, STAT3, and MAPK, three distinct signal pathways in prostate cancer cells,” Biochemical and Biophysical Research Communications, vol. 305, no. 3, pp. 462–469, 2003. View at Publisher · View at Google Scholar · View at Scopus
  137. Y.-S. Pu, T.-C. Hour, S.-E. Chuang, A.-L. Cheng, M.-K. Lai, and M.-L. Kuo, “Interleukin-6 is responsible for drug resistance and anti-apoptotic effects in prostatic cancer cells,” Prostate, vol. 60, no. 2, pp. 120–129, 2004. View at Publisher · View at Google Scholar · View at Scopus
  138. Y. Liu, P.-K. Li, C. Li, and J. Lin, “Inhibition of STAT3 signaling blocks the anti-apoptotic activity of IL-6 in human liver cancer cells,” The Journal of Biological Chemistry, vol. 285, no. 35, pp. 27429–27439, 2010. View at Publisher · View at Google Scholar · View at Scopus
  139. C. Liu, Y. Zhu, W. Lou, Y. Cui, C. P. Evans, and A. C. Gao, “Inhibition of constitutively active Stat3 reverses enzalutamide resistance in LNCaP derivative prostate cancer cells,” The Prostate, vol. 74, no. 2, pp. 201–209, 2014. View at Publisher · View at Google Scholar
  140. B. Paule, S. Terry, L. Kheuang, P. Soyeux, F. Vacherot, and A. de Taille, “The NF-κB/IL-6 pathway in metastatic androgen-independent prostate cancer: new therapeutic approaches?” World Journal of Urology, vol. 25, no. 5, pp. 477–489, 2007. View at Publisher · View at Google Scholar · View at Scopus
  141. D. J. Wang, A. Legesse-Miller, E. L. Johnson, and H. A. Coller, “Regulation of the let-7a-3 promoter by NF-κB,” PLoS ONE, vol. 7, no. 2, Article ID e31240, 2012. View at Publisher · View at Google Scholar · View at Scopus
  142. S. Rose-John, G. H. Waetzig, J. Cheller, J. Grötzinger, and D. Seegert, “The IL-6/sIL-6R complex as a novel target for therapeutic approaches,” Expert Opinion on Therapeutic Targets, vol. 11, no. 5, pp. 613–624, 2007. View at Publisher · View at Google Scholar · View at Scopus
  143. K. Rajalingam, R. Schreck, U. R. Rapp, and Š. Albert, “Ras oncogenes and their downstream targets,” Biochimica et Biophysica Acta: Molecular Cell Research, vol. 1773, no. 8, pp. 1177–1195, 2007. View at Publisher · View at Google Scholar · View at Scopus
  144. A. Fernández-Medarde and E. Santos, “Ras in cancer and developmental diseases,” Genes and Cancer, vol. 2, no. 3, pp. 344–358, 2011. View at Publisher · View at Google Scholar · View at Scopus
  145. P. Gideon, J. John, M. Frech et al., “Mutational and kinetic analyses of the GTPase-activating protein (GAP)-p21 interaction: the C-terminal domain of GAP is not sufficient for full activity,” Molecular and Cellular Biology, vol. 12, no. 5, pp. 2050–2056, 1992. View at Google Scholar · View at Scopus
  146. K. Scheffzek, M. R. Ahmadian, W. Kabsch et al., “The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic ras mutants,” Science, vol. 277, no. 5324, pp. 333–338, 1997. View at Publisher · View at Google Scholar · View at Scopus
  147. S. Schubbert, K. Shannon, and G. Bollag, “Hyperactive Ras in developmental disorders and cancer,” Nature Reviews Cancer, vol. 7, no. 4, pp. 295–308, 2007. View at Publisher · View at Google Scholar · View at Scopus
  148. N. Gerits, S. Kostenko, A. Shiryaev, M. Johannessen, and U. Moens, “Relations between the mitogen-activated protein kinase and the cAMP-dependent protein kinase pathways: comradeship and hostility,” Cellular Signalling, vol. 20, no. 9, pp. 1592–1607, 2008. View at Publisher · View at Google Scholar · View at Scopus
  149. A. S. Dhillon, S. Hagan, O. Rath, and W. Kolch, “MAP kinase signalling pathways in cancer,” Oncogene, vol. 26, no. 22, pp. 3279–3290, 2007. View at Publisher · View at Google Scholar · View at Scopus
  150. G. A. Repasky, E. J. Chenette, and C. J. Der, “Renewing the conspiracy theory debate: does Raf function alone to mediate Ras oncogenesis?” Trends in Cell Biology, vol. 14, no. 11, pp. 639–647, 2004. View at Publisher · View at Google Scholar · View at Scopus
  151. E. Castellano and J. Downward, “Ras interaction with PI3K: more than just another effector pathway,” Genes & Cancer, vol. 2, no. 3, pp. 261–274, 2011. View at Publisher · View at Google Scholar · View at Scopus
  152. J. A. Engelman, J. Luo, and L. C. Cantley, “The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism,” Nature Reviews Genetics, vol. 7, no. 8, pp. 606–619, 2006. View at Publisher · View at Google Scholar · View at Scopus
  153. B. S. Taylor, N. Schultz, H. Hieronymus et al., “Integrative genomic profiling of human prostate cancer,” Cancer Cell, vol. 18, no. 1, pp. 11–22, 2010. View at Publisher · View at Google Scholar · View at Scopus
  154. J. A. Engelman, “The role of phosphoinositide 3-kinase pathway inhibitors in the treatment of lung cancer,” Clinical Cancer Research, vol. 13, no. 15, part 2, pp. S4637–S4640, 2007. View at Publisher · View at Google Scholar · View at Scopus
  155. M. A. Davies, “Regulation, role, and targeting of Akt in cancer,” Journal of Clinical Oncology, vol. 29, no. 35, pp. 4715–4717, 2011. View at Publisher · View at Google Scholar · View at Scopus
  156. V. Poulaki, C. S. Mitsiades, C. McMullan et al., “Regulation of vascular endothelial growth factor expression by insulin-like growth factor I in thyroid carcinomas,” The Journal of Clinical Endocrinology & Metabolism, vol. 88, no. 11, pp. 5392–5398, 2003. View at Publisher · View at Google Scholar · View at Scopus
  157. G. Niu, K. L. Wright, M. Huang et al., “Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis,” Oncogene, vol. 21, no. 13, pp. 2000–2008, 2002. View at Publisher · View at Google Scholar · View at Scopus
  158. L. Guo, C. Chen, M. Shi et al., “Stat3-coordinated Lin-28-let-7-HMGA2 and miR-200-ZEB1 circuits initiate and maintain oncostatin M-driven epithelial-mesenchymal transition,” Oncogene, vol. 32, no. 45, pp. 5272–5282, 2013. View at Google Scholar
  159. M. Colombatti, S. Grasso, A. Porzia et al., “The prostate specific membrane antigen regulates the expression of IL-6 and CCL5 in prostate tumour cells by activating the MAPK pathways,” PLoS ONE, vol. 4, no. 2, Article ID e4608, 2009. View at Publisher · View at Google Scholar
  160. K. Bouchelouche, P. L. Choyke, and J. Capala, “Prostate specific membrane antigen- a target for imaging and therapy with radionuclides,” Discovery Medicine, vol. 9, no. 44, pp. 55–61, 2010. View at Google Scholar · View at Scopus
  161. T. Naka, N. Nishimoto, and T. Kishimoto, “The paradigm of IL-6: from basic science to medicine,” Arthritis Research & Therapy, vol. 4, supplement 3, pp. S233–S242, 2002. View at Google Scholar
  162. F. Yu, H. Yao, P. Zhu et al., “let-7 regulates self renewal and tumorigenicity of breast cancer cells,” Cell, vol. 131, no. 6, pp. 1109–1123, 2007. View at Publisher · View at Google Scholar · View at Scopus
  163. W. Wahli and E. Martinez, “Superfamily of steroid nuclear receptors: positive and negative regulators of gene expression,” The FASEB Journal, vol. 5, no. 9, pp. 2243–2249, 1991. View at Google Scholar · View at Scopus
  164. C. J. Brown, S. J. Goss, D. B. Lubahn et al., “Androgen receptor locus on the human X chromosome: regional localization to Xq11-12 and description of a DNA polymorphism,” The American Journal of Human Genetics, vol. 44, no. 2, pp. 264–269, 1989. View at Google Scholar · View at Scopus
  165. E. P. Gelmann, “Molecular biology of the androgen receptor,” Journal of Clinical Oncology, vol. 20, no. 13, pp. 3001–3015, 2002. View at Publisher · View at Google Scholar · View at Scopus
  166. P. J. Roche, S. A. Hoare, and M. G. Parker, “A consensus DNA-binding site for the androgen receptor,” Molecular Endocrinology, vol. 6, no. 12, pp. 2229–2235, 1992. View at Publisher · View at Google Scholar · View at Scopus
  167. F. Claessens, G. Verrijdt, E. Schoenmakers et al., “Selective DNA binding by the androgen receptor as a mechanism for hormone-specific gene regulation,” The Journal of Steroid Biochemistry and Molecular Biology, vol. 76, no. 1–5, pp. 23–30, 2001. View at Publisher · View at Google Scholar · View at Scopus
  168. P. E. Lonergan and D. J. Tindall, “Androgen receptor signaling in prostate cancer development and progression,” Journal of Carcinogenesis, vol. 10, article 20, 2011. View at Publisher · View at Google Scholar · View at Scopus
  169. A. I. So, A. Hurtado-Coll, and M. E. Gleave, “Androgens and prostate cancer,” World Journal of Urology, vol. 21, no. 5, pp. 325–337, 2003. View at Publisher · View at Google Scholar · View at Scopus
  170. M. A. Titus, B. Zeithaml, B. Kantor et al., “Dominant-negative androgen receptor inhibition of intracrine androgen-dependent growth of castration-recurrent prostate cancer,” PLoS ONE, vol. 7, no. 1, Article ID e30192, 2012. View at Publisher · View at Google Scholar · View at Scopus
  171. J. A. Locke, E. S. Guns, A. A. Lubik et al., “Androgen Levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer,” Cancer Research, vol. 68, no. 15, pp. 6407–6415, 2008. View at Publisher · View at Google Scholar · View at Scopus
  172. M.-L. Zhu and N. Kyprianou, “Androgen receptor and growth factor signaling cross-talk in prostate cancer cells,” Endocrine-Related Cancer, vol. 15, no. 4, pp. 841–849, 2008. View at Publisher · View at Google Scholar · View at Scopus
  173. Z. Guo and Y. Qiu, “A new trick of an old molecule: androgen receptor splice variants taking the stage?!,” International Journal of Biological Sciences, vol. 7, no. 6, pp. 815–822, 2011. View at Google Scholar · View at Scopus
  174. K. Eisermann, C. J. Broderick, A. Bazarov, M. M. Moazam, and G. C. Fraizer, “Androgen up-regulates vascular endothelial growth factor expression in prostate cancer cells via an Sp1 binding site,” Molecular Cancer, vol. 12, no. 1, article 7, 2013. View at Publisher · View at Google Scholar · View at Scopus
  175. P. Saxena, M. Trerotola, T. Wang et al., “PSA regulates androgen receptor expression in prostate cancer cells,” Prostate, vol. 72, no. 7, pp. 769–776, 2012. View at Publisher · View at Google Scholar · View at Scopus
  176. G. Attard, C. S. Cooper, and J. S. de Bono, “Steroid hormone receptors in prostate cancer: a hard habit to break?” Cancer Cell, vol. 16, no. 6, pp. 458–462, 2009. View at Publisher · View at Google Scholar · View at Scopus
  177. R. Tummala, N. Nadiminty, W. Lou et al., “Lin28 promotes growth of prostate cancer cells and activates the androgen receptor,” The American Journal of Pathology, vol. 183, no. 1, pp. 288–295, 2013. View at Publisher · View at Google Scholar · View at Scopus