miR-146a-5p enhances hepatitis B virus replication through autophagy to promote aggravation of chronic hepatitis B

Abstract

The objective of this study was to investigate the mechanism by which miR-146a-5p mediated autophagy and hepatitis B virus (HBV) replication. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the mRNA expression levels of miR-146a-5p and X-linked inhibitor of apoptosis (XIAP) and HBV DNA and RNA. The protein expression levels of XIAP, IκB-α, murine double minute 2 oncoprotein (MDM2) and p53, the phosphorylation of p65, and the conversion of light chain 3 (LC3)-I to LC3-II were detected by Western blotting. The expression levels of XIAP, HBV-related pro-inflammatory cytokines, and serum markers were detected by enzyme-linked immunosorbent assay (ELISA). miR-146a-5p was highly expressed in patients with chronic hepatitis B (CHB) and HBV-expressing hepatocytes. HBV core protein (HBc) and HBV X protein (HBx) were responsible for its effects on miR-146a-5p expression through the nuclear factor-κB pathway. Furthermore, the miR-146a-5p inhibitor suppressed autophagic response and HBV replication as well as MDM2/p53 expression. Luciferase reporter assay confirmed that XIAP was a direct target of miR-146a-5p. We therefore demonstrated that miR-146a-5p mediated positive feedback loop by regulating autophagy-induced HBV replication via targeting the XIAP-mediated MDM2/p53 axis. © 2019 IUBMB Life, 71(9):1336–1346, 2019.