miR-146a-5p enhances hepatitis B virus replication through autophagy to promote aggravation of chronic hepatitis B.
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.
['Fu|Lei|L|', 'Fu|Xiaoyu|X|', 'Mo|Juan|J|', 'Li|Xiaomei|X|', 'Li|Ronghua|R|', 'Peng|Shifang|S|0000-0001-5923-4029']
D000818:Animals D001343:Autophagy D002460:Cell Line D005260:Female D056945:Hep G2 Cells D006515:Hepatitis B virus D019694:Hepatitis B, Chronic D022781:Hepatocytes D006801:Humans D008297:Male D051379:Mice D035683:MicroRNAs D008869:Microtubule-Associated Proteins D000072000:NF-KappaB Inhibitor alpha D051736:Proto-Oncogene Proteins c-mdm2 D015398:Signal Transduction D015534:Trans-Activators D054334:Viral Regulatory and Accessory Proteins D014779:Virus Replication D051636:X-Linked Inhibitor of Apoptosis Protein
miR-146a-5p autophagy XIAP chronic hepatitis B HBV replication