Pan Yongjie, Dai Jinhua, Liao Yufeng, Yu Qiuyun
Pharmazie. 2017 Sep 1;72(9):550-554. doi: 10.1691/ph.2017.7594.
Hepatitis B virus (HBV) infection is one of the most important infectious diseases in China. In this study, we investigated the functional role of miR-137 in HBV infection to further elucidate the mechanism underlying the associated pathology. Viral replication was determined after transfection of HEK293 cells with the replication-competent vector pHBV1.3 and miR137 mimics or inhibitors. Expression of HBV genes was determined by quantitative real-time PCR (qRT-PCR). Expression of miR-137 and protein inhibitor of activated STAT 2 (PIAS2) was determined by qRT-PCR and Western blotting. Activity of the PIAS2 3'-UTR was determined by dual-luciferase reporter assays. Transfection of HEK293 cells with pHBV1.3 increased the expression of miR-137. Co-transfection with miR-137 mimic upregulated HBV gene expression and viral replication. MiR-137 targeted the PIAS2 3'-UTR, and suppressed PIAS2 mRNA and protein expressions. SiRNA-mediated PIAS2 knockdown suppressed HBV gene expression and viral replication. PIAS2 expression rescued the promotion effect of miR-137 on HBV expression and viral replication. MiR-137 expression was significantly upregulated following HBV infection. Furthermore, miR-137 promoted the expression of HBV genes and viral replication by targeting the expression of PIAS2. Our findings might provide a new insight into the diagnosis and treatment of HBV infection.
乙型肝炎病毒（HBV）感染是中国最重要的传染病之一。在本研究中，我们调查了miR-137在HBV感染中的功能作用，以进一步阐明相关病理的潜在机制。在用具有复制能力的载体pHBV1.3和miR137模拟物或抑制剂转染HEK293细胞后，测定病毒复制情况。通过定量实时PCR（qRT-PCR）测定HBV基因的表达。通过qRT-PCR和蛋白质印迹法测定miR-137和信号转导和转录激活因子2（STAT2）的蛋白抑制剂（PIAS2）的表达。通过双荧光素酶报告基因测定法测定PIAS2 3'-UTR的活性。用pHBV1.3转染HEK293细胞可增加miR-137的表达。与miR-137模拟物共转染可上调HBV基因表达和病毒复制。miR-137靶向PIAS2 3'-UTR，并抑制PIAS2 mRNA和蛋白表达。小干扰RNA（SiRNA）介导的PIAS2基因敲低可抑制HBV基因表达和病毒复制。PIAS2表达挽救了miR-137对HBV表达和病毒复制的促进作用。HBV感染后miR-137表达显著上调。此外，miR-137通过靶向PIAS2的表达促进HBV基因的表达和病毒复制。我们的研究结果可能为HBV感染的诊断和治疗提供新的见解。
