The IL-6/STAT3 pathway upregulates microRNA-125b expression in hepatitis C virus infection
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Chia-Yen Dai1,2,3,4,5,6,*, Yi-Shan Tsai1,*, Wen-Wen Chou1, Tawei Liu1, Chung-Feng Huang1,2,4, Shu-Chi Wang3, Pei-Chien Tsai1, Ming-Lun Yeh1,4,5, Ming-Yen Hsieh1, Ching-I Huang1,5, Shang-Yin Vanson Liu7, Jee-Fu Huang1,4, Wan-Long Chuang1,4,6 and Ming-Lung Yu1,2,3,4,5,6,8
1Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
2Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
3Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
4Faculty of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
5Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
6Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
7Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung, Taiwan
8Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
*These authors contributed equally to this work
Ming-Lung Yu, email: firstname.lastname@example.org
Keywords: miR-125b; HCV; IL-6; STAT3; HCV
Received: July 28, 2017 Accepted: December 01, 2017 Published: January 10, 2018
Background/Aims: MicroRNA-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.
Results: High 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 Methods: HCV 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.
Conclusions: 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.
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