miR-146a-5p Enhances Hepatitis B Virus Replication Through Autophagy to Promote Aggravation of Chronic Hepatitis B.

Authors:
Lei Fu
Lei Fu
School of Pharmacy
China
Xiaoyu Fu
Xiaoyu Fu
Huazhong Agricultural University
China
Juan Mo
Juan Mo
Henan Agricultural University
China
Xiaomei Li
Xiaomei Li
Peking University
China
Ronghua Li
Ronghua Li
Cincinnati Children's Hospital Medical Center
United States
Shifang Peng
Shifang Peng
Emory University
United States

IUBMB Life 2019 Apr 24. Epub 2019 Apr 24.

Department of Infectious Diseases, Key Laboratory of Hunan Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan, China.

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, 2019.

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http://dx.doi.org/10.1002/iub.2044DOI Listing
April 2019
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References

(Supplied by CrossRef)
Serum levels of miRNA in patients with hepatitis B virus‐associated acute‐on‐chronic liver failure
Wen Y. et al.
HBPD INT 2018
Upregulation of microRNA‐146a by hepatitis B virus X protein contributes to hepatitis development by downregulating complement factor H
Li J. F. et al.
MBio 2015
XIAP underlies apoptosis resistance of renal cell carcinoma cells
Wen Z. Y. et al.
Mol. Med. Rep. 2018

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