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BioMed Research International
Volume 2016 (2016), Article ID 3956485, 13 pages
http://dx.doi.org/10.1155/2016/3956485
Review Article

Hepatoepigenetic Alterations in Viral and Nonviral-Induced Hepatocellular Carcinoma

1Division of Hepatology and Liver Research, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Observatory 7925, Western Cape, South Africa
2MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK

Received 2 October 2016; Accepted 30 November 2016

Academic Editor: Jeroen T. Buijs

Copyright © 2016 Mankgopo M. Kgatle 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. S. S. Thorgeirsson and J. W. Grisham, “Molecular pathogenesis of human hepatocellular carcinoma,” Nature Genetics, vol. 31, no. 4, pp. 339–346, 2002. View at Publisher · View at Google Scholar · View at Scopus
  2. R. L. Siegel, K. D. Miller, and A. Jemal, “Cancer statistics, 2015,” CA: A Cancer Journal for Clinicians, vol. 65, no. 1, pp. 5–29, 2015. View at Publisher · View at Google Scholar · View at Scopus
  3. H. B. El-Serag, “Epidemiology of viral hepatitis and hepatocellular carcinoma,” Gastroenterology, vol. 142, pp. 1264–1273. e1, 2012. View at Google Scholar
  4. S. Mittal and H. B. El-Serag, “Epidemiology of hepatocellular carcinoma: consider the population,” Journal of Clinical Gastroenterology, vol. 47, supplement, pp. S2–S6, 2013. View at Google Scholar · View at Scopus
  5. Y. Kondo, L. Shen, S. Suzuki et al., “Alterations of DNA methylation and histone modifications contribute to gene silencing in hepatocellular carcinomas,” Hepatology Research, vol. 37, no. 11, pp. 974–983, 2007. View at Publisher · View at Google Scholar · View at Scopus
  6. B. Li, W. Liu, L. Wang et al., “CpG island methylator phenotype associated with tumor recurrence in tumor-node-metastasis stage I hepatocellular carcinoma,” Annals of Surgical Oncology, vol. 17, no. 7, pp. 1917–1926, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. S. B. Baylin and J. E. Ohm, “Epigenetic gene silencing in cancer—a mechanism for early oncogenic pathway addiction?” Nature Reviews Cancer, vol. 6, no. 2, pp. 107–116, 2006. View at Publisher · View at Google Scholar · View at Scopus
  8. P. A. Jones and S. B. Baylin, “The epigenomics of cancer,” Cell, vol. 128, no. 4, pp. 683–692, 2007. View at Publisher · View at Google Scholar · View at Scopus
  9. P. A. Jones and S. B. Baylin, “The fundamental role of epigenetic events in cancer,” Nature Reviews Genetics, vol. 3, no. 6, pp. 415–428, 2002. View at Google Scholar · View at Scopus
  10. P. A. Jones and P. W. Laird, “Cancer epigenetics comes of age,” Nature Genetics, vol. 21, no. 2, pp. 163–167, 1999. View at Publisher · View at Google Scholar · View at Scopus
  11. A. P. Bird, “CpG-rich islands and the function of DNA methylation,” Nature, vol. 321, no. 6067, pp. 209–213, 1986. View at Publisher · View at Google Scholar · View at Scopus
  12. P. A. Jones and D. Takai, “The role of DNA methylation in mammalian epigenetics,” Science, vol. 293, no. 5532, pp. 1068–1070, 2001. View at Publisher · View at Google Scholar · View at Scopus
  13. J. J. Issa, “Epigenetics in cancer: what's the future?” Oncology, vol. 25, p. 220, 2011. View at Google Scholar
  14. C. Ozen, G. Yildiz, A. T. Dagcan et al., “Genetics and epigenetics of liver cancer,” New Biotechnology, vol. 30, no. 4, pp. 381–384, 2013. View at Publisher · View at Google Scholar · View at Scopus
  15. S. Ito, A. C. Dalessio, O. V. Taranova, K. Hong, L. C. Sowers, and Y. Zhang, “Role of tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification,” Nature, vol. 466, no. 7310, pp. 1129–1133, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. R. M. Kohli and Y. Zhang, “TET enzymes, TDG and the dynamics of DNA demethylation,” Nature, vol. 502, no. 7472, pp. 472–479, 2013. View at Publisher · View at Google Scholar · View at Scopus
  17. T. Jenuwein and C. D. Allis, “Translating the histone code,” Science, vol. 293, no. 5532, pp. 1074–1080, 2001. View at Publisher · View at Google Scholar · View at Scopus
  18. J. Govin, C. Caron, C. Lestrat, S. Rousseaux, and S. Khochbin, “The role of histones in chromatin remodelling during mammalian spermiogenesis,” European Journal of Biochemistry, vol. 271, no. 17, pp. 3459–3469, 2004. View at Publisher · View at Google Scholar · View at Scopus
  19. J. Nakayama, J. C. Rice, B. D. Strahl, C. D. Allis, and S. I. S. Grewal, “Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly,” Science, vol. 292, no. 5514, pp. 110–113, 2001. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Rea, F. Eisenhaber, D. O'Carroll et al., “Regulation of chromatin structure by site-specific histone H3 methyltransferases,” Nature, vol. 406, pp. 593–599, 2000. View at Publisher · View at Google Scholar · View at Scopus
  21. R. D. Kornberg and Y. Lorch, “Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome,” Cell, vol. 98, no. 3, pp. 285–294, 1999. View at Publisher · View at Google Scholar · View at Scopus
  22. A. Kirmizis, S. M. Bartley, A. Kuzmichev et al., “Silencing of human polycomb target genes is associated with methylation of histone H3 Lys 27,” Genes and Development, vol. 18, no. 13, pp. 1592–1605, 2004. View at Publisher · View at Google Scholar · View at Scopus
  23. D. Bonenfant, M. Coulot, H. Towbin, P. Schindler, and J. van Oostrum, “Characterization of histone H2A and H2B variants and their post-translational modifications by mass spectrometry,” Molecular and Cellular Proteomics, vol. 5, no. 3, pp. 541–552, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. C. L. Peterson and M.-A. Laniel, “Histones and histone modifications,” Current Biology, vol. 14, no. 14, pp. R546–R551, 2004. View at Publisher · View at Google Scholar · View at Scopus
  25. X. Li and X. Zhao, “Epigenetic regulation of mammalian stem cells,” Stem Cells and Development, vol. 17, no. 6, pp. 1043–1052, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. X. Li and X. Zhao, “Comprehensive review: stem cells and development,” Stem Cells and Development, vol. 17, no. 6, pp. 1043–1052, 2008. View at Publisher · View at Google Scholar
  27. M. G. Lee, R. Villa, P. Trojer et al., “Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination,” Science, vol. 318, no. 5849, pp. 447–450, 2007. View at Publisher · View at Google Scholar · View at Scopus
  28. R. Cao, L. Wang, H. Wang et al., “Role of histone H3 lysine 27 methylation in polycomb-group silencing,” Science, vol. 298, no. 5595, pp. 1039–1043, 2002. View at Publisher · View at Google Scholar · View at Scopus
  29. D. P. F. Tsang and A. S. L. Cheng, “Epigenetic regulation of signaling pathways in cancer: role of the histone methyltransferase EZH2,” Journal of Gastroenterology and Hepatology, vol. 26, no. 1, pp. 19–27, 2011. View at Publisher · View at Google Scholar · View at Scopus
  30. M. Sasaki, H. Ikeda, K. Itatsu et al., “The overexpression of polycomb group proteins Bmi1 and EZH2 is associated with the progression and aggressive biological behavior of hepatocellular carcinoma,” Laboratory Investigation, vol. 88, no. 8, pp. 873–882, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. A. M. Farcas, N. P. Blackledge, I. Sudbery et al., “KDM2B links the polycomb repressive complex 1 (PRC1) to recognition of CpG islands,” eLife, vol. 2012, no. 1, Article ID e00205, 2012. View at Publisher · View at Google Scholar · View at Scopus
  32. L. Tavares, E. Dimitrova, D. Oxley et al., “RYBP-PRC1 complexes mediate H2A ubiquitylation at polycomb target sites independently of PRC2 and H3K27me3,” Cell, vol. 148, pp. 664–678, 2012. View at Google Scholar
  33. J. K. Stock, S. Giadrossi, M. Casanova et al., “Ring1-mediated ubiquitination of H2A restrains poised RNA polymerase II at bivalent genes in mouse ES cells,” Nature Cell Biology, vol. 9, no. 12, pp. 1428–1435, 2007. View at Publisher · View at Google Scholar · View at Scopus
  34. S.-J. Park, J.-G. Kim, T. G. Son et al., “The histone demethylase JMJD1A regulates adrenomedullin-mediated cell proliferation in hepatocellular carcinoma under hypoxia,” Biochemical and Biophysical Research Communications, vol. 434, no. 4, pp. 722–727, 2013. View at Publisher · View at Google Scholar · View at Scopus
  35. C. M. Croce, “Causes and consequences of microRNA dysregulation in cancer,” Nature Reviews Genetics, vol. 10, no. 10, pp. 704–714, 2009. View at Publisher · View at Google Scholar · View at Scopus
  36. M. Esteller, “Non-coding RNAs in human disease,” Nature Reviews Genetics, vol. 12, no. 12, pp. 861–874, 2011. View at Publisher · View at Google Scholar · View at Scopus
  37. E. C. Lai, “Predicting and validating microRNA targets,” Genome Biology, vol. 5, no. 9, article no. 115, 2004. View at Publisher · View at Google Scholar · View at Scopus
  38. T. Du and P. D. Zamore, “microPrimer: the biogenesis and function of microRNA,” Development, vol. 132, no. 21, pp. 4645–4652, 2005. View at Publisher · View at Google Scholar · View at Scopus
  39. E. Berezikov and R. H. A. Plasterk, “Camels and zebrafish, viruses and cancer: a microRNA update,” Human Molecular Genetics, vol. 14, no. 2, pp. R183–R190, 2005. View at Publisher · View at Google Scholar · View at Scopus
  40. N. Valeri, I. Vannini, F. Fanini, F. Calore, B. Adair, and M. Fabbri, “Epigenetics, miRNAs, and human cancer: a new chapter in human gene regulation,” Mammalian Genome, vol. 20, no. 9-10, pp. 573–580, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. 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
  42. O. C. Araújo, A. S. Rosa, A. Fernandes et al., “RASSF1A and DOK1 promoter methylation levels in hepatocellular carcinoma, cirrhotic and non-cirrhotic liver, and correlation with liver cancer in brazilian patients,” PLOS ONE, vol. 11, no. 4, Article ID e0153796, 2016. View at Publisher · View at Google Scholar
  43. J. Chen, J. Zhao, R. Ma, H. Lin, X. Liang, and X. Cai, “Prognostic significance of E-cadherin expression in hepatocellular carcinoma: a meta-analysis,” PLoS ONE, vol. 9, no. 8, Article ID e103952, 2014. View at Publisher · View at Google Scholar · View at Scopus
  44. L. Hu, G. Chen, H. Yu, and X. Qiu, “Clinicopathological significance of RASSF1A reduced expression and hypermethylation in hepatocellular carcinoma,” Hepatology International, vol. 4, no. 1, pp. 423–432, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. Z.-H. Zhao, Y.-C. Fan, Y. Yang, and K. Wang, “Association between Ras association domain family 1A promoter methylation and hepatocellular carcinoma: a meta-analysis,” World Journal of Gastroenterology, vol. 19, no. 41, pp. 7189–7196, 2013. View at Publisher · View at Google Scholar · View at Scopus
  46. Y.-M. Li, S.-C. Xu, J. Li et al., “Epithelial-mesenchymal transition markers expressed in circulating tumor cells in hepatocellular carcinoma patients with different stages of disease,” Cell Death & Disease, vol. 4, no. 10, article e831, 2013. View at Publisher · View at Google Scholar · View at Scopus
  47. X. Q. Wang, W. Zhang, E. L. H. Lui et al., “Notch1-Snail1-E-cadherin pathway in metastatic hepatocellular carcinoma,” International Journal of Cancer, vol. 131, no. 3, pp. E163–E172, 2012. View at Publisher · View at Google Scholar · View at Scopus
  48. C.-N. Guan, X.-M. Chen, H.-Q. Lou, X.-H. Liao, B.-Y. Chen, and P.-W. Zhang, “Clinical significance of axin and β-catenin protein expression in primary hepatocellular carcinomas,” Asian Pacific Journal of Cancer Prevention, vol. 13, no. 2, pp. 677–681, 2012. View at Publisher · View at Google Scholar · View at Scopus
  49. R. C. Zhao, J. Zhou, J. Y. He, Y. G. Wei, Y. Qin, and B. Li, “Aberrant promoter methylation of SOCS-1 gene may contribute to the pathogenesis of hepatocellular carcinoma: a meta-analysis,” Journal of BUON, vol. 21, pp. 142–151, 2016. View at Google Scholar
  50. Z. Qu, Y. Jiang, H. Li, D.-C. Yu, and Y.-T. Ding, “Detecting abnormal methylation of tumor suppressor genes GSTP1, P16, RIZ1, and RASSF1A in hepatocellular carcinoma and its clinical significance,” Oncology Letters, vol. 10, no. 4, pp. 2553–2558, 2015. View at Publisher · View at Google Scholar · View at Scopus
  51. A. Villanueva, A. Portela, S. Sayols et al., “DNA methylation-based prognosis and epidrivers in hepatocellular carcinoma,” Hepatology, vol. 61, no. 6, pp. 1945–1956, 2015. View at Publisher · View at Google Scholar · View at Scopus
  52. Y. Saito, Y. Kanai, M. Sakamoto, H. Saito, H. Ishii, and S. Hirohashi, “Overexpression of a splice variant of DNA methyltransferase 3b, DNMT3b4, associated with DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 15, pp. 10060–10065, 2002. View at Publisher · View at Google Scholar · View at Scopus
  53. T. Oda, H. Tsuda, M. Sakamoto, and S. Hirohashi, “Different mutations of the p53 gene in nodule-in-nodule hepatocellular carcinoma as a evidence for multistage progression,” Cancer Letters, vol. 83, no. 1-2, pp. 197–200, 1994. View at Publisher · View at Google Scholar · View at Scopus
  54. P. Laurent-Puig and J. Zucman-Rossi, “Genetics of hepatocellular tumors,” Oncogene, vol. 25, no. 27, pp. 3778–3786, 2006. View at Publisher · View at Google Scholar · View at Scopus
  55. S. M. Mazzoni and E. R. Fearon, “AXIN1 and AXIN2 variants in gastrointestinal cancers,” Cancer Letters, vol. 355, no. 1, pp. 1–8, 2014. View at Publisher · View at Google Scholar · View at Scopus
  56. M. Klasić, J. Krištić, P. Korać et al., “DNA hypomethylation upregulates expression of the MGAT3 gene in HepG2 cells and leads to changes in N-glycosylation of secreted glycoproteins,” Scientific Reports, vol. 6, Article ID 24363, 2016. View at Publisher · View at Google Scholar
  57. S. O. Sajadian, S. Ehnert, H. Vakilian et al., “Induction of active demethylation and 5hmC formation by 5-azacytidine is TET2 dependent and suggests new treatment strategies against hepatocellular carcinoma,” Clinical Epigenetics, vol. 7, no. 1, article 98, 2015. View at Publisher · View at Google Scholar · View at Scopus
  58. S. L.-K. Au, C. C.-L. Wong, J. M.-F. Lee, C.-M. Wong, and I. O.-L. Ng, “EZH2-mediated H3K27me3 is involved in epigenetic repression of deleted in liver cancer 1 in human cancers,” PLoS ONE, vol. 8, no. 6, Article ID e68226, 2013. View at Publisher · View at Google Scholar · View at Scopus
  59. M.-Y. Cai, Z.-T. Tong, F. Zheng et al., “EZH2 protein: a promising immunomarker for the detection of hepatocellular carcinomas in liver needle biopsies,” Gut, vol. 60, no. 7, pp. 967–976, 2011. View at Publisher · View at Google Scholar · View at Scopus
  60. F. Rappa, A. Greco, C. Podrini et al., “Correction: immunopositivity for histone MacroH2A1 isoforms marks steatosis-associated hepatocellular carcinoma,” PLOS ONE, vol. 8, no. 3, 2013. View at Publisher · View at Google Scholar · View at Scopus
  61. M. Borghesan, C. Fusilli, F. Rappa et al., “DNA Hypomethylation and histone variant macroH2A1 synergistically attenuate chemotherapy-induced senescence to promote hepatocellular carcinoma progression,” Cancer Research, vol. 76, no. 3, pp. 594–606, 2016. View at Publisher · View at Google Scholar · View at Scopus
  62. S. Jueliger, J. Lyons, S. Cannito et al., “Efficacy and epigenetic interactions of novel DNA hypomethylating agent guadecitabine (SGI-110) in preclinical models of hepatocellular carcinoma,” Epigenetics, vol. 11, no. 10, pp. 709–720, 2016. View at Publisher · View at Google Scholar
  63. S.-B. Gao, B. Xu, L.-H. Ding et al., “The functional and mechanistic relatedness of EZH2 and menin in hepatocellular carcinoma,” Journal of Hepatology, vol. 61, no. 4, pp. 832–839, 2014. View at Publisher · View at Google Scholar · View at Scopus
  64. S.-B. Gao, Q.-F. Zheng, B. Xu et al., “EZH2 represses target genes through H3K27-dependent and H3K27-independent mechanisms in hepatocellular carcinoma,” Molecular Cancer Research, vol. 12, no. 10, pp. 1388–1397, 2014. View at Publisher · View at Google Scholar · View at Scopus
  65. C.-R. Xie, Z. Li, H.-G. Sun et al., “Mutual regulation between CHD5 and EZH2 in hepatocellular carcinoma,” Oncotarget, vol. 6, no. 38, pp. 40940–40952, 2015. View at Publisher · View at Google Scholar · View at Scopus
  66. A. Hayashi, N. Yamauchi, J. Shibahara et al., “Concurrent activation of acetylation and tri-methylation of H3K27 in a subset of hepatocellular carcinoma with aggressive behavior,” PLoS ONE, vol. 9, no. 3, Article ID e91330, 2014. View at Publisher · View at Google Scholar · View at Scopus
  67. K. Bai, Y. Cao, C. Huang, J. Chen, X. Zhang, and Y. Jiang, “Association of histone methyltransferase G9a and overall survival after liver resection of patients with hepatocellular carcinoma with a median observation of 40 months,” Medicine, vol. 95, no. 2, Article ID e2493, 2016. View at Publisher · View at Google Scholar · View at Scopus
  68. C. Li, M. Cai, L. Jiang et al., “CLDN14 is epigenetically silenced by EZH2-mediated H3K27ME3 and is a novel prognostic biomarker in hepatocellular carcinoma,” Carcinogenesis, vol. 37, no. 6, pp. 557–566, 2016. View at Publisher · View at Google Scholar
  69. L. Jiang, Y.-D. Yang, L. Fu et al., “CLDN3 inhibits cancer aggressiveness via Wnt-EMT signaling and is a potential prognostic biomarker for hepatocellular carcinoma,” Oncotarget, vol. 5, no. 17, pp. 7663–7676, 2014. View at Publisher · View at Google Scholar · View at Scopus
  70. S. Hino, K. Kohrogi, and M. Nakao, “Histone demethylase LSD1 controls the phenotypic plasticity of cancer cells,” Cancer Science, vol. 107, no. 9, pp. 1187–1192, 2016. View at Publisher · View at Google Scholar
  71. A. Sakamoto, S. Hino, K. Nagaoka et al., “Lysine demethylase LSD1 coordinates glycolytic and mitochondrial metabolism in hepatocellular carcinoma cells,” Cancer Research, vol. 75, no. 7, pp. 1445–1456, 2015. View at Publisher · View at Google Scholar · View at Scopus
  72. D. Yamada, S. Kobayashi, H. Yamamoto et al., “Role of the hypoxia-related gene, JMJD1A, in hepatocellular carcinoma: clinical impact on recurrence after hepatic resection,” Annals of Surgical Oncology, vol. 19, no. 3, pp. S355–S364, 2012. View at Publisher · View at Google Scholar · View at Scopus
  73. J. T. Buijs, G. Van Der Horst, C. Van Den Hoogen et al., “The BMP2/7 heterodimer inhibits the human breast cancer stem cell subpopulation and bone metastases formation,” Oncogene, vol. 31, no. 17, pp. 2164–2174, 2012. View at Publisher · View at Google Scholar · View at Scopus
  74. M. Khalaf, J. Morera, A. Bourret et al., “BMP system expression in GCs from polycystic ovary syndrome women and the in vitro effects of BMP4, BMP6, and BMP7 on GC steroidogenesis,” European Journal of Endocrinology, vol. 168, no. 3, pp. 437–444, 2013. View at Publisher · View at Google Scholar · View at Scopus
  75. H. P. H. Naber, TGF-Beta and BMP in Breast Cancer Cell Invasion, Signal Transduction and Ageing Section, Department of Molecular Cell Biology, Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University, 2012.
  76. X. Ji, S. Jin, X. Qu et al., “Lysine-specific demethylase 5C promotes hepatocellular carcinoma cell invasion through inhibition BMP7 expression,” BMC Cancer, vol. 15, no. 1, article no. 801, 2015. View at Publisher · View at Google Scholar · View at Scopus
  77. M. R. Zou, J. Cao, Z. Liu, S. J. Huh, K. Polyak, and Q. Yan, “Histone demethylase Jumonji AT-rich Interactive Domain 1B (JARID1B) controls mammary gland development by regulating key developmental and lineage specification genes,” Journal of Biological Chemistry, vol. 289, no. 25, pp. 17620–17633, 2014. View at Publisher · View at Google Scholar · View at Scopus
  78. X.-X. He, S.-Z. Kuang, J.-Z. Liao et al., “The regulation of microRNA expression by DNA methylation in hepatocellular carcinoma,” Molecular BioSystems, vol. 11, no. 2, pp. 532–539, 2015. View at Publisher · View at Google Scholar · View at Scopus
  79. Z. Liu, J. Wang, Y. Mao, B. Zou, and X. Fan, “MicroRNA-101 suppresses migration and invasion via targeting vascular endothelial growth factor-C in hepatocellular carcinoma cells,” Oncology Letters, vol. 11, no. 1, pp. 433–438, 2016. View at Publisher · View at Google Scholar · View at Scopus
  80. L. Lin, H. Liang, Y. Wang et al., “MicroRNA-141 inhibits cell proliferation and invasion and promotes apoptosis by targeting hepatocyte nuclear factor-3β in hepatocellular carcinoma cells,” BMC Cancer, vol. 14, no. 1, article no. 879, 2014. View at Publisher · View at Google Scholar · View at Scopus
  81. S.-L. Zhang and L. Liu, “microRNA-148a inhibits hepatocellular carcinoma cell invasion by targeting sphingosine-1-phosphate receptor 1,” Experimental and Therapeutic Medicine, vol. 9, no. 2, pp. 579–584, 2015. View at Publisher · View at Google Scholar · View at Scopus
  82. B. Deng, L. Qu, J. Li et al., “MiRNA-211 suppresses cell proliferation, migration and invasion by targeting SPARC in human hepatocellular carcinoma,” Scientific Reports, vol. 6, article 26679, 2016. View at Publisher · View at Google Scholar
  83. G. Chen, L. Lu, C. Liu, L. Shan, and D. Yuan, “MicroRNA-377 suppresses cell proliferation and invasion by inhibiting TIAM1 expression in hepatocellular carcinoma,” PLoS ONE, vol. 10, no. 3, Article ID e0117714, 2015. View at Publisher · View at Google Scholar · View at Scopus
  84. K. Sun, T. Zeng, D. Huang et al., “MicroRNA-431 inhibits migration and invasion of hepatocellular carcinoma cells by targeting the ZEB1-mediated epithelial-mensenchymal transition,” FEBS Open Bio, vol. 5, pp. 900–907, 2015. View at Publisher · View at Google Scholar · View at Scopus
  85. J. H. Noh, Y. G. Chang, M. G. Kim et al., “MiR-145 functions as a tumor suppressor by directly targeting histone deacetylase 2 in liver cancer,” Cancer Letters, vol. 335, no. 2, pp. 455–462, 2013. View at Publisher · View at Google Scholar · View at Scopus
  86. Y. Zeng, X. Liang, G. Zhang et al., “miRNA-135a promotes hepatocellular carcinoma cell migration and invasion by targeting forkhead box O1,” Cancer Cell International, vol. 16, no. 1, 2016. View at Publisher · View at Google Scholar
  87. K. Liu, S. Liu, W. Zhang et al., “miR-494 promotes cell proliferation, migration and invasion, and increased sorafenib resistance in hepatocellular carcinoma by targeting PTEN,” Oncology Reports, vol. 34, no. 2, pp. 1003–1010, 2015. View at Publisher · View at Google Scholar · View at Scopus
  88. 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
  89. Y. Wang, H. C. Toh, P. Chow et al., “MicroRNA-224 is up-regulated in hepatocellular carcinoma through epigenetic mechanisms,” FASEB Journal, vol. 26, no. 7, pp. 3032–3041, 2012. View at Publisher · View at Google Scholar · View at Scopus
  90. 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
  91. D. M. Pereira, P. M. Rodrigues, P. M. Borralho, and C. M. P. Rodrigues, “Delivering the promise of miRNA cancer therapeutics,” Drug Discovery Today, vol. 18, no. 5-6, pp. 282–289, 2013. View at Publisher · View at Google Scholar · View at Scopus
  92. J. S. Tuttleman, C. Pourcel, and J. Summers, “Formation of the pool of covalently closed circular viral DNA in hepadnavirus-infected cells,” Cell, vol. 47, no. 3, pp. 451–460, 1986. View at Publisher · View at Google Scholar · View at Scopus
  93. M. S. Chapman and L. Liljas, “Structural folds of viral proteins,” Advances in Protein Chemistry, vol. 64, pp. 125–196, 2003. View at Publisher · View at Google Scholar · View at Scopus
  94. N. Paran, A. Cooper, and Y. Shaul, “Interaction of hepatitis B virus with cells,” Reviews in Medical Virology, vol. 13, no. 3, pp. 137–143, 2003. View at Publisher · View at Google Scholar · View at Scopus
  95. W.-K. Sung, H. Zheng, S. Li et al., “Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma,” Nature Genetics, vol. 44, no. 7, pp. 765–769, 2012. View at Publisher · View at Google Scholar · View at Scopus
  96. M. A. Feitelson and J. Lee, “Hepatitis B virus integration, fragile sites, and hepatocarcinogenesis,” Cancer Letters, vol. 252, no. 2, pp. 157–170, 2007. View at Publisher · View at Google Scholar · View at Scopus
  97. Z. Jiang, S. Jhunjhunwala, J. Liu et al., “The effects of hepatitis B virus integration into the genomes of hepatocellular carcinoma patients,” Genome Research, vol. 22, no. 4, pp. 593–601, 2012. View at Publisher · View at Google Scholar · View at Scopus
  98. P. Vivekanandan, H. D.-J. Daniel, R. Kannangai, F. Martinez-Murillo, and M. Torbenson, “Hepatitis B virus replication induces methylation of both host and viral DNA,” Journal of Virology, vol. 84, no. 9, pp. 4321–4329, 2010. View at Publisher · View at Google Scholar · View at Scopus
  99. S. Lee, H. J. Lee, J.-H. Kim, H.-S. Lee, J. J. Jang, and G. H. Kang, “Aberrant CpG island hypermethylation along multistep hepatocarcinogenesis,” The American Journal of Pathology, vol. 163, no. 4, pp. 1371–1378, 2003. View at Publisher · View at Google Scholar · View at Scopus
  100. M.-P. Lambert, A. Paliwal, T. Vaissière et al., “Aberrant DNA methylation distinguishes hepatocellular carcinoma associated with HBV and HCV infection and alcohol intake,” Journal of Hepatology, vol. 54, no. 4, pp. 705–715, 2011. View at Publisher · View at Google Scholar · View at Scopus
  101. F. H. T. Duong, V. Christen, S. Lin, and M. H. Heim, “Hepatitis C virus-induced up-regulation of protein phosphatase 2A inhibits histone modification and DNA damage repair,” Hepatology, vol. 51, no. 3, pp. 741–751, 2010. View at Publisher · View at Google Scholar · View at Scopus
  102. Y.-J. Kim, J. K. Jung, S. Y. Lee, and K. L. Jang, “Hepatitis B virus X protein overcomes stress-induced premature senescence by repressing p16INK4aexpression via DNA methylation,” Cancer Letters, vol. 288, no. 2, pp. 226–235, 2010. View at Publisher · View at Google Scholar · View at Scopus
  103. Y. Edamoto, A. Hara, W. Biernat et al., “Alterations of RB1, p53 and Wnt pathways in hepatocellular carcinomas associated with hepatitis C, hepatitis B and alcoholic liver cirrhosis,” International Journal of Cancer, vol. 106, no. 3, pp. 334–341, 2003. View at Publisher · View at Google Scholar · View at Scopus
  104. J. K. Jung, S.-H. Park, and K. L. Jang, “Hepatitis B virus X protein overcomes the growth-inhibitory potential of retinoic acid by downregulating retinoic acid receptor-β2 expression via DNA methylation,” Journal of General Virology, vol. 91, no. 2, pp. 493–500, 2010. View at Publisher · View at Google Scholar · View at Scopus
  105. J. K. Jung, P. Arora, J. S. Pagano, and L. J. Kyung, “Expression of DNA methyltransferase 1 is activated by hepatitis B virus X protein via a regulatory circuit involving the p16INK4a-cyclin D1-CDK 4/6-pRb-E2F1 pathway,” Cancer Research, vol. 67, no. 12, pp. 5771–5778, 2007. View at Publisher · View at Google Scholar · View at Scopus
  106. D.-L. Zheng, L. Zhang, N. Cheng et al., “Epigenetic modification induced by hepatitis B virus X protein via interaction with de novo DNA methyltransferase DNMT3A,” Journal of Hepatology, vol. 50, no. 2, pp. 377–387, 2009. View at Publisher · View at Google Scholar · View at Scopus
  107. C. Zhang, X. Chen, H. Liu et al., “Alpha fetoprotein mediates HBx induced carcinogenesis in the hepatocyte cytoplasm,” International Journal of Cancer, vol. 137, no. 8, pp. 1818–1829, 2015. View at Publisher · View at Google Scholar · View at Scopus
  108. G. Barreto, A. Schäfer, J. Marhold et al., “Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation,” Nature, vol. 445, no. 7128, pp. 671–675, 2007. View at Publisher · View at Google Scholar · View at Scopus
  109. W. Guo, Z. Dong, Y. Guo, Z. Chen, G. Kuang, and Z. Yang, “Methylation-mediated repression of GADD45A and GADD45G expression in gastric cardia adenocarcinoma,” International Journal of Cancer, vol. 133, no. 9, pp. 2043–2053, 2013. View at Publisher · View at Google Scholar · View at Scopus
  110. J. Yan, Q. Lu, J. Dong, X. Li, K. Ma, and L. Cai, “Hepatitis B virus X protein suppresses caveolin-1 expression in hepatocellular carcinoma by regulating DNA methylation,” BMC Cancer, vol. 12, article no. 353, 2012. View at Publisher · View at Google Scholar · View at Scopus
  111. E. Y. Ting Tse, F. C. Fat Ko, E. K. Kwan Tung et al., “Caveolin-1 overexpression is associated with hepatocellular carcinoma tumourigenesis and metastasis,” Journal of Pathology, vol. 226, no. 4, pp. 645–653, 2012. View at Publisher · View at Google Scholar · View at Scopus
  112. J. Kwong, L. S.-N. Chow, A. Y.-H. Wong et al., “Epigenetic inactivation of the deleted in lung and esophageal cancer 1 gene in nasopharyngeal carcinoma,” Genes, Chromosomes and Cancer, vol. 46, no. 2, pp. 171–180, 2007. View at Publisher · View at Google Scholar · View at Scopus
  113. J. Kwong, J.-Y. Lee, K.-K. Wong et al., “Candidate tumor-suppressor gene DLEC1 is frequently downregulated by promoter hypermethylation and histone hypoacetylation in human epithelial ovarian cancer,” Neoplasia, vol. 8, no. 4, pp. 268–278, 2006. View at Publisher · View at Google Scholar · View at Scopus
  114. G.-H. Qiu, M. Salto-Tellez, J. A. Ross et al., “The tumor suppressor gene DLEC1 is frequently silenced by DNA methylation in hepatocellular carcinoma and induces G1 arrest in cell cycle,” Journal of Hepatology, vol. 48, no. 3, pp. 433–441, 2008. View at Publisher · View at Google Scholar · View at Scopus
  115. I. Y. Park, B. H. Sohn, E. Yu et al., “Aberrant epigenetic modifications in hepatocarcinogenesis induced by hepatitis B virus X protein,” Gastroenterology, vol. 132, no. 4, pp. 1476–1494, 2007. View at Publisher · View at Google Scholar · View at Scopus
  116. T. Hanafusa, Y. Yumoto, K. Nouso et al., “Reduced expression of insulin-like growth factor binding protein-3 and its promoter hypermethylation in human hepatocellular carcinoma,” Cancer Letters, vol. 176, no. 2, pp. 149–158, 2002. View at Publisher · View at Google Scholar · View at Scopus
  117. J.-Y. Yao, L. Zhang, X. Zhang et al., “H3K27 trimethylation is an early epigenetic event of p16INK4a silencing for regaining tumorigenesis in fusion reprogrammed hepatoma cells,” Journal of Biological Chemistry, vol. 285, no. 24, pp. 18828–18837, 2010. View at Publisher · View at Google Scholar · View at Scopus
  118. Y.-H. Shim, G.-S. Yoon, H.-J. Choi, Y. H. Chung, and E. Yu, “p16 hypermethylation in the early stage of hepatitis B virus-associated hepatocarcinogenesis,” Cancer Letters, vol. 190, no. 2, pp. 213–219, 2003. View at Publisher · View at Google Scholar · View at Scopus
  119. Y.-Z. Zhu, R. Zhu, J. Fan et al., “Hepatitis B virus X protein induces hypermethylation of p16INK4A promoter via DNA methyltransferases in the early stage of HBV-associated hepatocarcinogenesis,” Journal of Viral Hepatitis, vol. 17, no. 2, pp. 98–107, 2010. View at Publisher · View at Google Scholar · View at Scopus
  120. R. Zhu, B.-Z. Li, H. Li et al., “Association of p16INK4A hypermethylation with hepatitis B virus X protein expression in the early stage of HBV-associated hepatocarcinogenesis,” Pathology International, vol. 57, no. 6, pp. 328–336, 2007. View at Publisher · View at Google Scholar · View at Scopus
  121. H. Fan, H. Zhang, P. E. Pascuzzi, and O. Andrisani, “Hepatitis B virus X protein induces EpCAM expression via active DNA demethylation directed by RelA in complex with EZH2 and TET2,” Oncogene, vol. 35, no. 6, pp. 715–726, 2016. View at Publisher · View at Google Scholar · View at Scopus
  122. S. L.-K. Au, C. C.-L. Wong, J. M.-F. Lee et al., “Enhancer of zeste homolog 2 epigenetically silences multiple tumor suppressor microRNAs to promote liver cancer metastasis,” Hepatology, vol. 56, no. 2, pp. 622–631, 2012. View at Publisher · View at Google Scholar · View at Scopus
  123. D. Li, X. Liu, L. Lin et al., “MicroRNA-99a inhibits hepatocellular carcinoma growth and correlates with prognosis of patients with hepatocellular carcinoma,” Journal of Biological Chemistry, vol. 286, no. 42, pp. 36677–36685, 2011. View at Publisher · View at Google Scholar · View at Scopus
  124. D. Ngo-Yin Fan, F. Ho-Ching Tsang, A. Hoi-Kam 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, vol. 57, no. 2, pp. 637–647, 2013. View at Publisher · View at Google Scholar · View at Scopus
  125. L. Wang, X. Zhang, L.-T. Jia et al., “C-Myc-mediated epigenetic silencing of microRNA-101 contributes to dysregulation of multiple pathways in hepatocellular carcinoma,” Hepatology, vol. 59, no. 5, pp. 1850–1863, 2014. View at Publisher · View at Google Scholar · View at Scopus
  126. F. Yu, Z. Lu, B. Chen, P. Dong, and J. Zheng, “microRNA-150: a promising novel biomarker for hepatitis B virus-related hepatocellular carcinoma,” Diagnostic Pathology, vol. 10, article no. 129, 2015. View at Publisher · View at Google Scholar · View at Scopus
  127. L. Rivière, L. Gerossier, A. Ducroux et al., “HBx relieves chromatin-mediated transcriptional repression of hepatitis B viral cccDNA involving SETDB1 histone methyltransferase,” Journal of Hepatology, vol. 63, no. 5, pp. 1093–1102, 2015. View at Publisher · View at Google Scholar · View at Scopus
  128. C. Cicchini, C. Battistelli, and M. Tripodi, “SETDB1 is a new promising target in HCC therapy,” Chinese Clinical Oncology, vol. 5, pp. 504–504, 2016. View at Publisher · View at Google Scholar
  129. Q. Fei, K. Shang, J. Zhang et al., “Histone methyltransferase SETDB1 regulates liver cancer cell growth through methylation of p53,” Nature Communications, vol. 6, article no. 8651, 2015. View at Publisher · View at Google Scholar
  130. T. Longerich, “Dysregulation of the epigenetic regulator SETDB1 in liver carcinogenesis—more than one way to skin a cat,” Chinese Clinical Oncology, vol. 5, pp. 318–318, 2016. View at Publisher · View at Google Scholar
  131. A. S. Lok, L. B. Seeff, T. R. Morgan et al., “Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease,” Gastroenterology, vol. 136, no. 1, pp. 138–148, 2009. View at Publisher · View at Google Scholar · View at Scopus
  132. F. Conti, F. Buonfiglioli, A. Scuteri et al., “Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals,” Journal of Hepatology, vol. 65, no. 4, pp. 727–733, 2016. View at Publisher · View at Google Scholar
  133. J. M. Llovet and A. Villanueva, “Liver cancer: effect of HCV clearance with direct-acting antiviral agents on HCC,” Nature Reviews Gastroenterology & Hepatology, vol. 13, no. 10, pp. 561–562, 2016. View at Publisher · View at Google Scholar
  134. M. Reig, Z. Mariño, C. Perelló et al., “Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy,” Journal of Hepatology, vol. 65, no. 4, pp. 719–726, 2016. View at Publisher · View at Google Scholar
  135. B. D. Lindenbach and C. Rice, “Flaviviridae: the viruses and their replication,” in Fields Virology, vol. 1, pp. 991–1041, Lippincott Williams & Wilkins, 2001. View at Google Scholar
  136. T. Heintges and J. R. Wands, “Hepatitis C virus: epidemiology and transmission,” Hepatology, vol. 26, no. 3, pp. 521–526, 1997. View at Publisher · View at Google Scholar · View at Scopus
  137. D. Moradpour, F. Penin, and C. M. Rice, “Replication of hepatitis C virus,” Nature Reviews Microbiology, vol. 5, no. 6, pp. 453–463, 2007. View at Publisher · View at Google Scholar · View at Scopus
  138. K. J. Blight, J. A. McKeating, J. Marcotrigiano, and C. M. Rice, “Efficient replication of hepatitis C virus genotype 1a RNAs in cell culture,” Journal of Virology, vol. 77, no. 5, pp. 3181–3190, 2003. View at Publisher · View at Google Scholar · View at Scopus
  139. L. Rongrui, H. Na, L. Zongfang, J. Fanpu, and J. Shiwen, “Epigenetic mechanism involved in the HBV/HCV-related hepatocellular carcinoma tumorigenesis,” Current Pharmaceutical Design, vol. 20, no. 11, pp. 1715–1725, 2014. View at Publisher · View at Google Scholar · View at Scopus
  140. Y.-B. Deng, G. Nagae, Y. Midorikawa et al., “Identification of genes preferentially methylated in hepatitis C virus-related hepatocellular carcinoma,” Cancer Science, vol. 101, no. 6, pp. 1501–1510, 2010. View at Publisher · View at Google Scholar · View at Scopus
  141. T. Hishiki, Y. Shimizu, R. Tobita et al., “Infectivity of hepatitis C virus is influenced by association with apolipoprotein E isoforms,” Journal of Virology, vol. 84, no. 22, pp. 12048–12057, 2010. View at Publisher · View at Google Scholar · View at Scopus
  142. P. Arora, E.-O. Kim, J. K. Jung, and K. L. Jang, “Hepatitis C virus core protein downregulates E-cadherin expression via activation of DNA methyltransferase 1 and 3b,” Cancer Letters, vol. 261, no. 2, pp. 244–252, 2008. View at Publisher · View at Google Scholar · View at Scopus
  143. S.-H. Park, J. S. Lim, S.-Y. Lim, I. Tiwari, and K. L. Jang, “Hepatitis C virus Core protein stimulates cell growth by down-regulating p16 expression via DNA methylation,” Cancer Letters, vol. 310, no. 1, pp. 61–68, 2011. View at Publisher · View at Google Scholar · View at Scopus
  144. G. Benegiamo, M. Vinciguerra, G. Mazzoccoli, A. Piepoli, A. Andriulli, and V. Pazienza, “DNA methyltransferases 1 and 3b expression in Huh-7 cells expressing HCV core protein of different genotypes,” Digestive Diseases and Sciences, vol. 57, no. 6, pp. 1598–1603, 2012. View at Publisher · View at Google Scholar · View at Scopus
  145. M. Ripoli, R. Barbano, T. Balsamo et al., “Hypermethylated levels of E-cadherin promoter in Huh-7 cells expressing the HCV core protein,” Virus Research, vol. 160, no. 1-2, pp. 74–81, 2011. View at Publisher · View at Google Scholar · View at Scopus
  146. H. Quan, F. Zhou, D. Nie et al., “Hepatitis C virus core protein epigenetically silences SFRP1 and enhances HCC aggressiveness by inducing epithelial-mesenchymal transition,” Oncogene, vol. 33, no. 22, pp. 2826–2835, 2014. View at Publisher · View at Google Scholar · View at Scopus
  147. K. C. Lakshmaiah, L. A. Jacob, S. Aparna, D. Lokanatha, and S. C. Saldanha, “Epigenetic therapy of cancer with histone deacetylase inhibitors,” Journal of Cancer Research and Therapeutics, vol. 10, no. 3, pp. 469–478, 2014. View at Publisher · View at Google Scholar · View at Scopus
  148. K. B. Glaser, “HDAC inhibitors: clinical update and mechanism-based potential,” Biochemical Pharmacology, vol. 74, no. 5, pp. 659–671, 2007. View at Publisher · View at Google Scholar · View at Scopus
  149. K. Tohyama, “Editorial [hot topic: new treatment strategy of the myelodysplastic syndromes],” Current Pharmaceutical Design, vol. 18, no. 22, pp. 3147–3148, 2012. View at Publisher · View at Google Scholar · View at Scopus
  150. E. A. Griffiths and S. D. Gore, “Epigenetic therapies in MDS and AML,” in Epigenetic Alterations in Oncogenesis, pp. 253–283, Springer, Berlin, Germany, 2013. View at Google Scholar
  151. Q. Mei, M. Chen, X. Lu et al., “An open-label, single-arm, phase I/II study of lower-dose decitabine based therapy in patients with advanced hepatocellular carcinoma,” Oncotarget, vol. 6, no. 18, pp. 16698–16711, 2015. View at Publisher · View at Google Scholar · View at Scopus
  152. S. Venturelli, A. Berger, T. Weiland et al., “Differential induction of apoptosis and senescence by the DNA methyltransferase inhibitors 5-azacytidine and 5-aza-2′-deoxycytidine in solid tumor cells,” Molecular Cancer Therapeutics, vol. 12, no. 10, pp. 2226–2236, 2013. View at Publisher · View at Google Scholar · View at Scopus
  153. S. Timmermann, P. W. Hinds, and K. Münger, “Re-expression of endogenous p16(ink4a) in oral squamous cell carcinoma lines by 5-aza-2'-deoxycytidine treatment induces a senescence-like state,” Oncogene, vol. 17, no. 26, pp. 3445–3453, 1998. View at Google Scholar · View at Scopus
  154. S.-I. Suh, H.-Y. Pyun, J.-W. Cho et al., “5-Aza-2′-deoxycytidine leads to down-regulation of aberrant p16INK4A RNA transcripts and restores the functional retinoblastoma protein pathway in hepatocellular carcinoma cell lines,” Cancer Letters, vol. 160, no. 1, pp. 81–88, 2000. View at Publisher · View at Google Scholar · View at Scopus
  155. K. B. Chiappinelli, C. A. Zahnow, N. Ahuja, and S. B. Baylin, “Combining epigenetic and immunotherapy to combat cancer,” Cancer Research, vol. 76, no. 7, pp. 1683–1689, 2016. View at Publisher · View at Google Scholar
  156. A. E. Dear, “Epigenetic modulators and the new immunotherapies,” The New England Journal of Medicine, vol. 374, no. 7, pp. 684–686, 2016. View at Publisher · View at Google Scholar · View at Scopus
  157. S. Venturelli, S. Armeanu, A. Pathil et al., “Epigenetic combination therapy as a tumor-selective treatment approach for hepatocellular carcinoma,” Cancer, vol. 109, no. 10, pp. 2132–2141, 2007. View at Publisher · View at Google Scholar · View at Scopus
  158. S. Venturelli, A. Berger, T. Weiland et al., “Dual antitumour effect of 5-azacytidine by inducing a breakdown of resistance-mediating factors and epigenetic modulation,” Gut, vol. 60, no. 2, pp. 156–165, 2011. View at Publisher · View at Google Scholar · View at Scopus
  159. Y. Kuang, A. El-Khoueiry, P. Taverna, M. Ljungman, and N. Neamati, “Guadecitabine (SGI-110) priming sensitizes hepatocellular carcinoma cells to oxaliplatin,” Molecular Oncology, vol. 9, no. 9, pp. 1799–1814, 2015. View at Publisher · View at Google Scholar · View at Scopus
  160. A. Ilyas, Z. Hashim, and S. Zarina, “Effects of 5′-azacytidine and alendronate on a hepatocellular carcinoma cell line: a proteomics perspective,” Molecular and Cellular Biochemistry, vol. 405, no. 1-2, pp. 53–61, 2015. View at Publisher · View at Google Scholar · View at Scopus
  161. V. M. Richon, J. Garcia-Vargas, and J. S. Hardwick, “Development of vorinostat: current applications and future perspectives for cancer therapy,” Cancer Letters, vol. 280, no. 2, pp. 201–210, 2009. View at Publisher · View at Google Scholar · View at Scopus
  162. L. Barbarotta and K. Hurley, “Romidepsin for the treatment of peripheral T-cell lymphoma,” Journal of the Advanced Practitioner in Oncology, vol. 6, no. 1, pp. 22–36, 2015. View at Google Scholar
  163. S. P. Iyer and F. F. Foss, “Romidepsin for the treatment of peripheral T-cell lymphoma,” Oncologist, vol. 20, no. 9, pp. 1084–1091, 2015. View at Publisher · View at Google Scholar · View at Scopus
  164. I.-T. Chiang, Y.-C. Liu, W.-H. Wang et al., “Sorafenib inhibits TPA-induced MMP-9 and VEGF expression via suppression of ERK/NF-kappaB pathway in hepatocellular carcinoma cells,” In Vivo, vol. 26, no. 4, pp. 671–681, 2012. View at Google Scholar · View at Scopus
  165. F.-T. Hsu, Y. -C. Liu, I.-T. Chiang et al., “Sorafenib increases efficacy of vorinostat against human hepatocellular carcinoma through transduction inhibition of vorinostat-induced ERK/NF-κB signaling,” International Journal of Oncology, vol. 45, no. 1, pp. 177–188, 2014. View at Publisher · View at Google Scholar · View at Scopus
  166. Food and Drug Administration, “Food and Drug Administration. FDA approves Beleodaq to treat rare, aggressive form of non-Hodgkin lymphoma. July 3, 2014,” FDA Approves Beleodaq to Treat Rare, Aggressive Form of Non-Hodgkin Lymphoma, July 2014.
  167. M. Mottamal, S. Zheng, T. L. Huang, and G. Wang, “Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents,” Molecules, vol. 20, no. 3, pp. 3898–3941, 2015. View at Publisher · View at Google Scholar · View at Scopus
  168. S. L. Chan, H. C. Chung, L. Wang et al., “Efficacy of belinostat in advanced hepatocellular carcinoma (HCC): phase I and II multicentered study of the mayo phase 2 consortium (P2C) and the cancer therapeutics research group (CTRG),” in Proceedings of the ASCO Annual Meeting Proceedings, p. 259, 2012.
  169. A. Milano, R. V. Iaffaioli, and F. Caponigro, “The proteasome: a worthwhile target for the treatment of solid tumours?” European Journal of Cancer, vol. 43, no. 7, pp. 1125–1133, 2007. View at Publisher · View at Google Scholar · View at Scopus
  170. J. L. Spratlin, T. M. Pitts, G. N. Kulikowski et al., “Synergistic activity of histone deacetylase and proteasome inhibition against pancreatic and hepatocellular cancer cell lines,” Anticancer Research, vol. 31, no. 4, pp. 1093–1103, 2011. View at Google Scholar · View at Scopus
  171. K. Weintraub, “Take two: combining immunotherapy with epigenetic drugs to tackle cancer,” Nature Medicine, vol. 22, no. 1, pp. 8–10, 2016. View at Publisher · View at Google Scholar · View at Scopus
  172. J. S. You and P. A. Jones, “Cancer genetics and epigenetics: two sides of the same coin?” Cancer Cell, vol. 22, no. 1, pp. 9–20, 2012. View at Publisher · View at Google Scholar · View at Scopus