The IL-6/STAT3 pathway upregulates microRNA-125b expression in hepatitis C virus infection.
The IL-6/STAT3 pathway upregulates microRNA-125b expression in hepatitis C virus infection.
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DOI：
10.18632/oncotarget.24129
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发表时间：
2018-02-16
期刊：
影响因子：
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通讯作者：
Yu ML
中科院分区：
文献类型：
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作者：
Dai CY;Tsai YS;Chou WW;Liu T;Huang CF;Wang SC;Tsai PC;Yeh ML;Hsieh MY;Huang CI;Vanson Liu SY;Huang JF;Chuang WL;Yu ML
MicroRNA-125b （miR-125b）已被发现在许多癌症中调节炎症并作为致癌基因。miR-125b在丙型肝炎病毒（HCV）感染过程中的表达机制尚不清楚。本研究旨在确定在HCV感染中可能调节miR-125b表达的因素。在复制子细胞和HCV感染患者的血清中发现miR-125b的高表达与HCV感染相关，而miR-125b抑制剂可降低HCV基因表达。白细胞介素6 (IL-6)/信号换能器和转录激活因子3 （STAT3）通路对miR-125b基因表达起诱导作用。STAT3 siRNA或抑制剂可减少HCV复制。用17-羟基jolkinolide B （HJB）或STAT3 siRNA处理HCV复制子细胞Con1 （1b型）和Huh7/Ava5 （1b型）。采用细胞活力测定和Renilla荧光素酶测定。构建miR-125b-1启动子片段用于荧光素酶报告基因检测。采用TaqMan®基因表达法检测PSMB8、PSMB9、miR-125b-1和miR-125b-2的表达。Western blot分析蛋白丰度。本研究阐明了miR-125b在慢性HCV感染发病机制中的新途径，并提示其可能是治疗HCV感染的靶点。
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. 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. 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. 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.