Repression of MicroRNA-30e by Hepatitis C Virus Enhances Fatty Acid Synthesis

Abstract

Chronic hepatitis C virus (HCV) infection often leads to end-stage liver disease, including hepatocellular carcinoma (HCC). We have previously observed reduced expression of microRNA-30e (miR-30e) in the liver tissues and sera of patients with HCV-associated HCC, although biological functions remain unknown. In this study, we demonstrated that HCV infection of hepatocytes transcriptionally reduces miR-30e expression by modulating CCAAT/enhancer binding protein β. In silico prediction suggests that autophagy-related gene 5 (ATG5) is a direct target of miR-30e. ATG5 is involved in autophagy biogenesis, and HCV infection in hepatocytes induces autophagy. We showed the presence of ATG5 in the miR-30e–Argonaute 2 RNA-induced silencing complex. Overexpression of miR-30e in HCV-infected hepatocytes inhibits autophagy activation. Subsequent studies suggested that ATG5 knockdown in Huh7.5 cells results in the remarkable inhibition of sterol regulatory element binding protein (SREBP)-1c and fatty acid synthase (FASN) level. We also showed that overexpression of miR-30e decreased lipid synthesis-related protein SREBP-1c and FASN in hepatocytes. Conclusion: We show new mechanistic insights into the interactions between autophagy and lipid synthesis through inhibition of miR-30e in HCV-infected hepatocytes.