MiR-122 modulates type I interferon expression through blocking suppressor of cytokine signaling 1
MiR-122 modulates type I interferon expression through blocking suppressor of cytokine signaling 1
复制标题
MiR-122 通过阻断细胞因子信号传导抑制因子 1 来调节 I 型干扰素表达
DOI：
10.1016/j.biocel.2013.01.008
复制
发表时间：
2013-04-01
影响因子：
4
通讯作者：
Zhang, Fengmin
中科院分区：
文献类型：
--
作者：
Li, Aimei;Song, Wuqi;Zhang, Fengmin
miR-122是一种肝脏特异性miRNA。最近的研究表明，干扰素（IFN）治疗丙型肝炎病毒（HCV）感染患者的疗效较差，肝脏中miR-122丰度较低。肝癌患者肝脏中的miR-122水平也较低。我们以前发现，当miR-122在人少突胶质细胞中被敲低时，IFN表达减少。其机制尚不清楚。本研究以miR-122丰富的Huh 7细胞为研究对象，探讨miR-122对I型IFN表达的调控机制。我们发现miR-122显著增加Huh 7细胞中I型IFN的表达，而敲低miR-122则降低I型IFN的表达。通过在IFN信号通路的负调控因子中筛选潜在的miR-122靶点，我们发现在细胞因子信号转导抑制因子1（SOCS 1）mRNA中存在推定的miR-122靶点。过表达miR-122使SOCS 1的表达降低50.55%，而敲低miR-122使SOCS 1的表达增加62.56%。使用绿色荧光蛋白（EGFP）融合的SOCS 1表达质粒，miR-122模拟物处理的细胞中SOCS 1-EGFP荧光强度和蛋白表达低于mock-miRNA处理的细胞，而miR-122敲低显著增加SOCS 1-EGFP荧光强度和蛋白表达。nt 359-nt 375区域的突变放弃了miR-122对SOCS 1-EGFP表达的影响。总之，SOCS 1是miR-122的靶点。miR-122可通过调节SOCS 1的表达来调节I型IFN的表达。(c)2013爱思唯尔有限公司保留所有权利。
MiR-122 is a liver-specific miRNA. Recent studies demonstrated that the interferon (IFN) therapy efficacy is poor in the hepatitis C virus (HCV)-infected patients with lower miR-122 abundance in the livers. The hepatocarcinoma patients also have low miR-122 levels in their livers. We previously found that the IFN expression was reduced when miR-122 was knocked down in human oligodendrocytes. The mechanism is unclear. In this study, the miR-122-abundant cell Huh7 was used to explore the regulatory mechanism of miR-122 on type I IFN expression. We found that miR-122 significantly increased the type I IFN expression in Huh7 cells, while knocking down miR-122 decreased the type I IFN expression. By screening potential miR-122 targets among the negative regulators in IFN signaling pathways, we found that there were putative miR-122 targets in the suppressor of cytokine signaling 1 (SOCS1) mRNA. Over-expressing miR-122 decreased the SOCS1 expression by 50.55% in Huh7 cells, while knocking down miR-122 increased SOCS1 expression by 62.56%. Using a green fluorescence protein (EGFP) fused SOCS1-expressing plasmid, the SOCS1-EGFP fluorescence intensity and protein were lower in miR-122 mimic-treated cells than those in mock-miRNA-treated cells, while miR-122 knockdown significantly increased the SOCS1-EGFP fluorescence intensity and protein expression. Mutations in the nt359-nt375 region abandoned the impact of miR-122 on SOCS1-EGFP expression. Taken together, SOCS1 is a target of miR-122. MiR-122 can regulate the type I IFN expression through modulating the SOCS1 expression. (c) 2013 Elsevier Ltd. All rights reserved.