Abstract
BackgroundHepatitis B virus (HBV) remains a major cause of chronic hepatitis and hepatocellular carcinoma, and miRNAs play important roles in HBV pathogenesis. Our previous study has shown that miR-328-3p is upregulated in HBV-infected patients and serves as a potent predictor for the prognosis of HBV-related liver failure.MethodsHere, the role of miR-328-3p in modulating cell injury in HBV-infected liver cells THLE-2 was investigated in detail. MiR-328-3p expression was examined using qRT-PCR. The levels of pro-inflammatory cytokines were measured using ELISA. HBV RNA and HBV DNA levels were quantified. The interactions between STAT3 and miR-328-3p promoter as well as miR-328-3p and FOXO4 were analyzed using chromatin immunoprecipitation (CHIP) assay and luciferase reporter assay, respectively. THLE-2 cell injury was evaluated by examining cell viability and apoptosis.ResultsHBV promoted expression of miR-328-3p through the STAT3 signal pathway and that increasingly expressed miR-328-3p downregulated its target FOXO4, leading to the promotion of cell injury in HBV-infected liver cells THLE-2.ConclusionThese data demonstrate that HBV-STAT3-miR-328-3p-FOXO4 regulation pathway may play an important role in the pathogenesis of HBV infection.
Highlights
Hepatitis B virus (HBV) remains a major cause of chronic hepatitis and hepatocellular carcinoma, and miRNAs play important roles in HBV pathogenesis
Our previous study showed that serum miR-146a-5p, miR-122-3p and miR-328-3p levels were upregulated in patients with acute-on-chronic liver failure (ACLF) and chronic hepatitis B (CHB) compared with the chronic asymptomatic HBV carriers (ASC) [9]
These results indicate that miR328-3p expression may correlate with enhanced inflammation in HB patients caused by HBV infection
Summary
Hepatitis B virus (HBV) remains a major cause of chronic hepatitis and hepatocellular carcinoma, and miRNAs play important roles in HBV pathogenesis. Our previous study showed that serum miR-146a-5p, miR-122-3p and miR-328-3p levels were upregulated in patients with acute-on-chronic liver failure (ACLF) and chronic hepatitis B (CHB) compared with the chronic asymptomatic HBV carriers (ASC) [9]. The increased levels of these three miRNAs positively correlate with the severity of liver inflammation in ACLF patients and may be useful to predict the severity of HBV-associated ACLF [9]. 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 previously demonstrated that miR-146a-5p enhances HBV
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