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miR‐370 suppresses HBV gene expression and replication by targeting nuclear factor IA
Author(s) -
Fan Hongxia,
Lv Ping,
Lv Jing,
Zhao Xiaopei,
Liu Min,
Zhang Guangling,
Tang Hua
Publication year - 2017
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.24695
Subject(s) - virology , biology , gene , replication (statistics) , viral replication , gene expression , virus , microbiology and biotechnology , genetics
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.