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miR‐146a‐5p enhances hepatitis B virus replication through autophagy to promote aggravation of chronic hepatitis B
Author(s) -
Fu Lei,
Fu Xiaoyu,
Mo Juan,
Li Xiaomei,
Li Ronghua,
Peng Shifang
Publication year - 2019
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.2044
Subject(s) - xiap , hbx , hepatitis b virus , microbiology and biotechnology , chemistry , viral replication , autophagy , virology , apoptosis , virus , biology , programmed cell death , biochemistry , caspase
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