期刊
ANTIVIRAL RESEARCH
卷 118, 期 -, 页码 20-28出版社
ELSEVIER
DOI: 10.1016/j.antiviral.2015.03.001
关键词
MicroRNA-122; Suppressor of cytokine signaling 3; Interferon; Hepatitis B virus; Hepatocytes
资金
- National Natural Science Foundation of China (NSFC) [J1103609, J1210062, 81402267, 81401660]
- Foundation of Heilongjiang Provincial Postdoctor of China [LBH-Z11086]
- Heilongjiang Province College Medical Etiology (BSL3) Key Laboratory Fund
- Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity, Harbin Medical University
MicroRNA-122 (miR-122) is involved in the pathogenesis of several liver diseases, including chronic hepatitis B infection and hepatocellular carcinoma. This study aimed to explore the potential role of miR-122 in the interferon (IFN)-mediated suppression of hepatitis B virus (HBV) in hepatocytes. We found that elevated expression of suppressor of cytokine signaling 3 (SOCS3) following HBV infection, contributed to the inactivation of the IFN signaling pathway. Based on previous studies from our laboratory showing that miR-122 can modulate type I IFN expression by inhibiting SOCS1 expression, we analyzed the SOCS3 mRNA sequence for putative miR-122 binding sites. We demonstrate that miR-122 inhibits SOCS3 expression by targeting the 3'-untranslated region of the SOCS3 mRNA within the region 1887 1910 nucleotides. Finally, we demonstrate that significantly increased levels of IFN lead to decreased HBV expression in miR-122 mimic-treated Huh7 cells, whereas inhibition of endogenous miR-122 leads to enhanced viral production, owing to a marked decrease in IFN expression. Taken together, our results demonstrate that miR-122 down-regulates SOCS3, thus positively affecting the anti-HBV efficiency of endogenous type I IFN. Our study suggests that suppression of miR-122 induced by HBV infection, leads to the inactivation of IFN expression, which in turn enhances HBV replication, contributing to viral persistence and hepatocarcinogenesis. (C) 2015 Published by Elsevier B.V.
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