Abstract
Background/AimsMicroRNA-125b (miR-125b) has been found to regulate inflammation and acts as an oncogene in many cancers. The mechanisms of miR-125b expression during hepatitis C virus (HCV) infection remain to be clarified. The present study aims to identify the factors that might regulate miR-125b expression in HCV infection.ResultsHigh expression of miR-125b was found to correlate with HCV infection in replicon cells and in sera from HCV-infected patients, whereas the miR-125b inhibitor reduced HCV gene expression. The interleukin 6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway plays an inducible effect on miR-125b gene expression. STAT3 siRNA or inhibitor could reduce HCV replication.Materials and MethodsHCV replicon cells Con1 (type 1b) and Huh7/Ava5 (type 1b) were treated with 17-hydroxy-jolkinolide B (HJB) or STAT3 siRNA. Cell viability assay and Renilla Luciferase Assay were used. Fragments of the miR-125b-1 promoter were constructed for the luciferase reporter assay. PSMB8, PSMB9, miR-125b-1, and miR-125b-2 expression was determined using TaqMan® Gene Expression Assays. Western blot analysis was performed to assess protein abundance.ConclusionsThis study elucidates a novel pathway for miR-125b in the pathogenesis of chronic HCV infection and suggests it as a possible target for treating HCV infection.
Highlights
Hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide, chronically affecting more than 170 million people [1,2,3]
This study elucidates a novel pathway for miR-125b in the pathogenesis of chronic HCV infection and suggests it as a possible target for treating HCV infection
We investigated the correlation between PSMB9 and miR-125b in HCV replicon cells to explore the biological roles of miR-125b in HCV replication through interleukin 6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway activation and repression of the antigen-presenting gene, PSMB9
Summary
Hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide, chronically affecting more than 170 million people [1,2,3]. In the United States and most other developed nations, the prevalence of HCV infection is 1–2%. Our previous studies in Taiwan have revealed some HCV-hyperendemic villages in the southern area with anti-HCV prevalence greater than 20% [4, 5]. All oral direct antiviral agents (DAAs) reported recently have a high cure rate, the current standard treatment in Taiwan and in some Asian countries involves combination therapy with pegylated interferon-α (PEG-IFN) and ribavirin (RBV) for patients www.impactjournals.com/oncotarget with chronic hepatitis C (CHC), with a relatively high sustained virologic response (SVR) rate of 75%–95% [6,7,8]. PEG-IFN/RBV remains the standard treatment in countries where DAAs are not yet available
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