The Role Of SRC-3in HBV Transcription And Replication

Hepatitis B is a worldwide contagious disease caused by Hepatitis B virus (HBV) infection. Chronic HBV infection tends to induce cirrhosis and hepatocellular carcinoma with high mortality. Steroid receptor co-activator3(SRC-3) is a member of the family of p160co-activators involved in cell metabolism and progression of HCC, and these proccesses are also highly related with replication of HBV, suggesting that SRC-3may have a role in HBV replication.In this study, we used hydrodynamic injection as animal model and found that after injection of HBV plasmid, the levels of HBV antigens in serum and HBV total mRNA in liver were significantly higher in SRC-3-/-mice, compared with WT mice. Down-regulatuion of SRC-3in HepG2cells could increase the expression of HBV mRNA and antigens after transfection of HBV plasmid. However, no significant influence from SRC-3was observed on the expression of anti-virus genes in HepG2cells. Thus SRC-3may regulate HBV replication on the transcription level. Phosphorylation of Akt was dampened in shSRC-3HepG2cells, and rescue of Akt phosphorylation could impair the enhancement of HBV expression. In addition, Phosphorylation level of Akt in liver tissues was lower in SRC-3-/-mice, compared with WT mice. Furthermore, SRC-3inhibited HNF-4a-induced HBV core promoter activity. All these evidences indicated that SRC-3negatively regulates HBV transcription, partially at least, through Akt signaling pathway which is related with the transcriptional activity of HNF-4a.