Epigenetic regulation of MicroRNA-122 by peroxisome proliferator activated receptor-gamma and hepatitis b virus X protein in hepatocellular carcinoma cells

• DOI: 10.1002/hep.26514
• Publication Date: 2013-05-23T22:05:10Z
• Authors: Kyoungsub Song; Chang Han; Jinqiang Zhang; Dongdong Lu; Srikanta Dash; Mark Feitelson; Kyu Lim; Tong Wu
• Keywords: MiR-122; Retinoid X receptor

MicroRNA-122 (miR-122), a pivotal liver-specific miRNA, has been implicated in several liver diseases including hepatocellular carcinoma (HCC) and hepatitis C B viral infection. This study aimed to explore epigenetic regulation of miR-122 human HCC cells examine the effect virus (HCV) (HBV). We performed microRNA microarray analysis identified as most up-regulated miRNA (6-fold) treated with 5′aza-2′deoxycytidine (5-Aza-CdR, DNA methylation inhibitor) 4-phenylbutyric acid (PBA, histone deacetylation inhibitor). Real-time polymerase chain reaction (PCR) verified significant up-regulation by 5′aza PBA cells, lesser extent primary hepatocytes. Peroxisome proliferator activated receptor-gamma (PPARγ) retinoid X receptor alpha (RXRα) complex was found be associated DR1 DR2 consensus site gene promoter which enhanced transcription. 5-Aza-CdR treatment increased association PPARγ/RXRα, but decreased its corepressors (N-CoR SMRT), motifs. The aforementioned DNA-protein also contains SUV39H1, an H3K9 methyl transferase, down-regulates expression. Conclusions: These findings establish novel role PPARγ binding for cells. Moreover, we show that protein binds inhibits transcription miR-122, whereas particles exhibited no effect; these provide mechanistic insight into reduction patients HBV not HCV (Hepatology 2013;58:1681–1692)