Histone Deacetylases and Their Regulatory MicroRNAs in Hepatocarcinogenesis

다국어 초록 (Multilingual Abstract)

A growing body of evidence suggests that epigenetic modifications are promising potential mechanisms in cancer research. Among the molecules that mediate epigenetic mechanisms, histone deacetylases (HDACs) are critical regulators of gene expression that promote formation of heterochromatin by deacetylating histone and non-histone proteins.

Aberrant regulation of HDACs contributes to malignant transformation and progression in a wide variety of human cancers, including hepatocellular carcinoma (HCC), gastric cancer, lung cancer, and other cancers. Thus, the roles of HDACs have been extensively studied because of their potential as therapeutic targets. However, the underlying mechanism leading to deregulation of individual HDACs remains largely unknown. Some reports have suggested that functional microRNAs (miRNAs) modulate epigenetic effector molecules including HDACs. Here, we describe the oncogenic or tumor suppressive functions of HDAC families and their regulatory miRNAs governing HDAC expression in hepatocarcinogenesis.

참고문헌 (Reference)

1 Zhang J, "microRNA-22, downregulated in hepatocellular carcinoma and correlated with prognosis, suppresses cell proliferation and tumourigenicity" 103 : 1215-1220, 2010

2 Liu Z, "miR-7 inhibits glioblastoma growth by simultaneously interfering with the PI3K/ATK and Raf/MEK/ERK pathways" 44 : 1571-1580, 2014

3 Pineau P, "miR-221 overexpression contributes to liver tumorigenesis" 107 : 264-269, 2010

4 Kota J, "Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model" 137 : 1005-1017, 2009

5 Wu J, "The up-regulation of histone deacetylase 8 promotes proliferation and inhibits apoptosis in hepatocellular carcinoma" 58 : 3545-3553, 2013

6 Whittaker S, "The role of signaling pathways in the development and treatment of hepatocellular carcinoma" 29 : 4989-5005, 2010

7 Yuan JH, "The histone deacetylase 4/SP1/microrna-200a regulatory network contributes to aberrant histone acetylation in hepatocellular carcinoma" 54 : 2025-2035, 2011

8 Liu M, "The genetic and epigenetic alterations in human hepatocellular carcinoma : a recent update" 5 : 673-691, 2014

9 Blander G, "The Sir2 family of protein deacetylases" 73 : 417-435, 2004

10 Yang XJ, "The Rpd3/Hda1 family of lysine deacetylases : from bacteria and yeast to mice and men" 9 : 206-218, 2008

11 Kim JK, "Targeted inactivation of HDAC2 restores p16INK4a activity and exerts antitumor effects on human gastric cancer" 11 : 62-73, 2013

12 Tajiri K, "Sneddon-Wilkinson disease induced by sorafenib in a patient with advanced hepatocellular carcinoma" 54 : 597-600, 2015

13 Kim JK, "Sirtuin7 oncogenic potential in human hepatocellular carcinoma and its regulation by the tumor suppressors MiR-125a-5p and MiR-125b" 57 : 1055-1067, 2013

14 Marquardt JU, "Sirtuin-6-dependent genetic and epigenetic alterations are associated with poor clinical outcome in hepatocellular carcinoma patients" 58 : 1054-1064, 2013

15 Chen J, "SIRT2 overexpression in hepatocellular carcinoma mediates epithelial to mesenchymal transition by protein kinase B/glycogen synthase kinase-3beta/beta-catenin signaling" 57 : 2287-2298, 2013

16 Maluccio M, "Recent progress in understanding, diagnosing, and treating hepatocellular carcinoma" 62 : 394-399, 2012

17 Peserico A, "Physical and functional HAT/HDAC interplay regulates protein acetylation balance" 2011 : 371832-, 2011

18 Esquela-Kerscher A, "Oncomirs-microRNAs with a role in cancer" 6 : 259-269, 2006

19 Nam SW, "Molecular changes from dysplastic nodule to hepatocellular carcinoma through gene expression profiling" 42 : 809-818, 2005

20 Bartel DP, "MicroRNAs: genomics, biogenesis, mechanism, and function" 116 : 281-297, 2004

21 Kim HS, "MicroRNA-31 functions as a tumor suppressor by regulating cell cycle and epithelial-mesenchymal transition regulatory proteins in liver cancer" 6 : 8089-8102, 2015

22 Bae HJ, "MicroRNA-29c functions as a tumor suppressor by direct targeting oncogenic SIRT1 in hepatocellular carcinoma" 33 : 2557-2567, 2014

23 Gramantieri L, "MicroRNA-221 targets Bmf in hepatocellular carcinoma and correlates with tumor multifocality" 15 : 5073-5081, 2009

24 Bae HJ, "MicroRNA-221 governs tumor suppressor HDAC6 to potentiate malignant progression of liver cancer" 63 : 408-419, 2015

25 Meng F, "MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer" 133 : 647-658, 2007

26 Wu J, "MicroRNA-188 suppresses G1/S transition by targeting multiple cyclin/CDK complexes" 12 : 66-, 2014

27 Fornari F, "MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma" 27 : 5651-5661, 2008

28 Noh JH, "MiR-145 functions as a tumor suppressor by directly targeting histone deacetylase 2 in liver cancer" 335 : 455-462, 2013

29 Datta J, "Methylation mediated silencing of MicroRNA-1 gene and its role in hepatocellular carcinogenesis" 68 : 5049-5058, 2008

30 Ford E, "Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription" 20 : 1075-1080, 2006

31 Elmén J, "LNA-mediated microRNA silencing in non-human primates" 452 : 896-899, 2008

32 Zhu P, "Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis" 5 : 455-463, 2004

33 Wu LM, "Identification of histone deacetylase 3 as a biomarker for tumor recurrence following liver transplantation in HBV-associated hepatocellular carcinoma" 5 : e14460-, 2010

34 Jung KH, "Histone deacetylase 6 functions as a tumor suppressor by activating c-Jun NH2-terminal kinase-mediated beclin 1-dependent autophagic cell death in liver cancer" 56 : 644-657, 2012

35 Tsochatzis EA, "Hepatocellular carcinoma" 366 : 92-, 2012

36 Noh JH, "HDAC2 provides a critical support to malignant progression of hepatocellular carcinoma through feedback control of mTORC1 and AKT" 74 : 1728-1738, 2014

37 Jung KH, "HDAC2 overexpression confers oncogenic potential to human lung cancer cells by deregulating expression of apoptosis and cell cycle proteins" 113 : 2167-2177, 2012

38 Xie HJ, "HDAC1 inactivation induces mitotic defect and caspase-independent autophagic cell death in liver cancer" 7 : e34265-, 2012

39 Jemal A, "Global cancer statistics" 61 : 69-90, 2011

40 Xiong Y, "Effects of microRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma" 51 : 836-845, 2010

41 Fan J, "Down-regulation of HDAC5 inhibits growth of human hepatocellular carcinoma by induction of apoptosis and cell cycle arrest" 35 : 11523-11532, 2014

42 Lachenmayer A, "Combination therapy for hepatocellular carcinoma : additive preclinical efficacy of the HDAC inhibitor panobinostat with sorafenib" 56 : 1343-1350, 2012

43 Rodriguez-Paredes M, "Cancer epigenetics reaches mainstream oncology" 17 : 330-339, 2011

44 Merlo LM, "Cancer as an evolutionary and ecological process" 6 : 924-935, 2006

45 Bolden JE, "Anticancer activities of histone deacetylase inhibitors" 5 : 769-784, 2006

46 Noh JH, "Aberrant regulation of HDAC2 mediates proliferation of hepatocellular carcinoma cells by deregulating expression of G1/S cell cycle proteins" 6 : e28103-, 2011