miR-370 suppresses HBV gene expression and replication by targeting nuclear factor IA.
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.
Tianjin Life Science Research Center and Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Hongxia
H
Fan
Tianjin Life Science Research Center and Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Ping
P
Lv
Tianjin Life Science Research Center and Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Jing
J
Lv
Tianjin Life Science Research Center and Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Xiaopei
X
Zhao
Tianjin Life Science Research Center and Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Min
M
Liu
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.
Guangling
G
Zhang
Tianjin Life Science Research Center and Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Hua
H
Tang
D002460:Cell Line; D015870:Gene Expression; D015967:Gene Expression Regulation, Viral; D055785:Gene Knockdown Techniques; D006515:Hepatitis B virus / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D051839:NFI Transcription Factors / Q000037:antagonists & inhibitors*; D014779:Virus Replication
C526503:MIRN370 microRNA, human; D035683:MicroRNAs; D051839:NFI Transcription Factors
HBV; NFIA; miR-370; microRNA; viral gene expression