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

Upregulation of microRNA-328-3p by hepatitis B virus contributes to THLE-2 cell injury by downregulating FOXO4

“…Among these three miRNAs, miR-146a-5p and miR-328-3p could distinguish ACLF from non-ACLF (ASC and CHB) with high values of specificity and sensitivity [9]. We have also previously demonstrated that miR-146a-5p enhances HBV replication through autophagy to promote aggravation of CHB [10]. MiR-146a has been shown to directly target CXCR4 [11], a gene involved in the advanced liver disease that is associated with hepatitis C virus or HBV [12].…”

MicroRNAs play an essential role in autophagy regulation in various disease phenotypes

“…miR-146a-5p promoted HBV replication through the XIAP-mediated MDM2 (mouse double minute 2 [MDM2])/p53 autophagy pathway to promote aggravation of chronic hepatitis B. 142 Enterovirus 71 (EV71) is a group of viruses that belongs to the Picornaviridae family and is the principal causative agent of severe and fatal hand, foot, and mouth disease. Overexpression of miR-30a could suppress EV71 replication by blocking EV71-induced autophagy.…”

“…p53 is one of the most intensively studied tumor suppressor proteins. miR‐146a‐5p promoted HBV replication through the XIAP‐mediated MDM2 (mouse double minute 2 [MDM2])/p53 autophagy pathway to promote aggravation of chronic hepatitis B …”

Plasma Level of ADAMTS13 or IL-12 as an Indicator of HBeAg Seroconversion in Chronic Hepatitis B Patients Undergoing m-ETV Treatment

“…The present cross-sectional observational study expressed that higher increasing ADAMTS13 and IL-12 levels, but not the baseline levels of ADAMTS13 and IL-12, were significantly and positively associated with the prevalence of HBeAg SC in CHB patients during 96-week m-ETV treatment, suggesting higher increasing plasma ADAMTS13 (IL-12) level as a definite probability for HBeAg SC, independent of other factors, such as HBV DNA, HBsAg, HBeAg, and VWF, although the VWF level is closely related to ADAMTS13 concentration in the peripheral blood of CHB patients. There are many literatures about the pathogenesis of patients with chronic HBV infection, and the imbalance of a coagulation system also plays an important role in CHB pathogenesis (Saray et al, 2012;Chang and Liu, 2016;Fu et al, 2019). Von Willebrand factor is a member of the main proteins involved in hemostasis and thrombosis in the body.…”