微小RNA-221通过下调细胞因子信号转导抑制因子1和细胞因子信号转导抑制因子3来增强干扰素的抗丙型肝炎病毒效应。
MiR-221 accentuates IFN׳s anti-HCV effect by downregulating SOCS1 and SOCS3.
作者信息
Xu Gang, Yang Fang, Ding Cui-Ling, Wang Jing, Zhao Ping, Wang Wen, Ren Hao
机构信息
Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, China.
Department of Hepatobiliary Surgery, Fuzhou General Hospital of Nanjing Military Area Command, Fuzhou 350025, China.
出版信息
Virology. 2014 Aug;462-463:343-50. doi: 10.1016/j.virol.2014.06.024. Epub 2014 Jul 12.
MiR-221 was reported to be upregulated and play roles in tumorigenesis of hepatitis C virus (HCV) associated hepatocellular carcinoma (HCC). However, the role of miR-221 in HCV infection remains unknown. In this study, it was found that miR-221 was upregulated in serum of HCV chronic hepatitis patients and Huh7.5.1 cells infected with HCVcc. Further studies indicated that miR-221 mimic could accentuate anti-HCV effect of IFN-α in HCVcc model, miR-221 mimic could further repressed 10% HCV RNA expression and 35-42% HCV core or NS5A protein expression in HCVcc infected Huh7.5.1 cells treated with 100IU/mL IFN-α, and miR-221 inhibitor resulted in the reverse effects. Furthermore, two members of suppressor of cytokine signaling (SOCS) family, SOCS1 and SOCS3, which are well established inhibitory factors on IFN/JAK/STAT pathway, were identified as the targets of miR-221 and were involved in the effect of miR-221. In conclusion, miR-221 could accentuate IFN׳s anti-HCV effect by targeting SOCS1 and SOCS3.
据报道，miR-221在丙型肝炎病毒（HCV）相关肝细胞癌（HCC）的肿瘤发生过程中表达上调并发挥作用。然而，miR-221在HCV感染中的作用仍不清楚。在本研究中，发现miR-221在HCV慢性肝炎患者血清以及感染HCVcc的Huh7.5.1细胞中表达上调。进一步研究表明，在HCVcc模型中，miR-221模拟物可增强IFN-α的抗HCV作用，在100IU/mL IFN-α处理的HCVcc感染的Huh7.5.1细胞中，miR-221模拟物可进一步抑制10%的HCV RNA表达以及35-42%的HCV核心蛋白或NS5A蛋白表达，而miR-221抑制剂则产生相反的效果。此外，细胞因子信号转导抑制因子（SOCS）家族的两个成员SOCS1和SOCS3，它们是IFN/JAK/STAT途径中公认的抑制因子，被确定为miR-221的靶标，并参与了miR-221的作用。总之，miR-221可通过靶向SOCS1和SOCS3增强IFN的抗HCV作用。
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