Down-regulation of suppressor of cytokine signaling 3 by miR-122 enhances interferon-mediated suppression of hepatitis B virus
Down-regulation of suppressor of cytokine signaling 3 by miR-122 enhances interferon-mediated suppression of hepatitis B virus
复制标题
miR-122 下调细胞因子信号传导 3 抑制因子可增强干扰素介导的乙型肝炎病毒抑制。
DOI：
10.1016/j.antiviral.2015.03.001
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发表时间：
2015-06-01
影响因子：
7.6
通讯作者：
Zhong, Zhaohua
中科院分区：
文献类型：
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作者：
Gao, Dongni;Zhai, Aixia;Zhong, Zhaohua
MicroRNA-122（miR-122）参与了多种肝脏疾病的发病机制，包括慢性B型肝炎感染和肝细胞癌。本研究旨在探讨miR-122在干扰素（IFN）介导的肝细胞抑制B型肝炎病毒（HBV）中的潜在作用。我们发现，HBV感染后细胞因子信号转导抑制因子3（SOCS 3）的表达升高，导致IFN信号通路的失活。基于我们实验室先前的研究表明miR-122可以通过抑制SOCS 1表达来调节I型IFN表达，我们分析了SOCS 3 mRNA序列中推定的miR-122结合位点。我们证明miR-122通过靶向SOCS 3 mRNA的3 '非翻译区1887 - 1910个核苷酸来抑制SOCS 3表达。最后，我们证明了IFN水平的显著增加导致miR-122模拟物处理的Huh 7细胞中HBV表达的降低，而内源性miR-122的抑制由于IFN表达的显著降低而导致病毒产生的增强。总之，我们的结果表明，miR-122下调SOCS 3，从而积极影响内源性I型IFN的抗HBV效率。我们的研究表明，HBV感染诱导的miR-122抑制导致IFN表达失活，这反过来又增强HBV复制，有助于病毒持续存在和肝癌发生。(C)2015年由Elsevier B. V.出版
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.