Tianjin Life Science Research Center and Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Tangshan Key Laboratory for Preclinical and Basic Research on Chronic Diseases, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, China.
J Med Virol. 2017 May;89(5):834-844. doi: 10.1002/jmv.24695. Epub 2016 Oct 3.
Hepatitis B virus (HBV) infection is a major health problem worldwide. The roles of microRNAs in the regulation of HBV expression are being increasingly recognized. In this study, we found that overexpression of miR-370 suppressed HBV gene expression and replication in Huh7 cells, whereas antisense knockdown of endogenous miR-370 enhanced HBV gene expression and replication in Huh7 cells and HepG2.2.15 cells. Further, we identified the transcription factor nuclear factor IA (NFIA) as a new host target of miR-370. Overexpression and knockdown studies showed that NFIA stimulated HBV gene expression and replication. Importantly, overexpression of NFIA counteracted the effect of miR-370 on HBV gene expression and replication. Further mechanistic studies showed that miR-370 suppressed HBV replication and gene expression by repressing HBV Enhancer I activity, and one of the NFIA binding site in the Enhancer I element was responsible for the repressive effect of miR-370 on HBV Enhancer I activity. Altogether, our results demonstrated that miR-370 suppressed HBV gene expression and replication through repressing NFIA expression, which stimulates HBV replication via direct regulation on HBV Enhancer I activities. Our findings may provide a new antiviral strategy for HBV infection. J. Med. Virol. 89:834-844, 2017. © 2016 Wiley Periodicals, Inc.
乙型肝炎病毒（HBV）感染是全球范围内的一个主要健康问题。miRNAs 在调节 HBV 表达中的作用正越来越受到关注。在本研究中，我们发现 miR-370 的过表达抑制了 Huh7 细胞中的 HBV 基因表达和复制，而内源性 miR-370 的反义敲低则增强了 Huh7 细胞和 HepG2.2.15 细胞中的 HBV 基因表达和复制。进一步，我们鉴定出转录因子核因子 IA（NFIA）是 miR-370 的一个新的宿主靶标。过表达和敲低研究表明，NFIA 刺激了 HBV 基因的表达和复制。重要的是，NFIA 的过表达抵消了 miR-370 对 HBV 基因表达和复制的影响。进一步的机制研究表明，miR-370 通过抑制 HBV 增强子 I 活性来抑制 HBV 复制和基因表达，而 Enhancer I 元件中的一个 NFIA 结合位点负责 miR-370 对 HBV Enhancer I 活性的抑制作用。总之，我们的研究结果表明，miR-370 通过抑制 NFIA 表达来抑制 HBV 基因表达和复制，而 NFIA 通过直接调节 HBV Enhancer I 活性来刺激 HBV 复制。我们的发现可能为 HBV 感染提供了一种新的抗病毒策略。J. Med. Virol. 89:834-844, 2017. © 2016 Wiley Periodicals, Inc.
