Modulation of HBV replication by microRNA-15b through targeting hepatocyte nuclear factor 1α.
Hepatitis B virus (HBV) infection remains a major health problem worldwide. The role played by microRNAs (miRNAs) in HBV replication and pathogenesis is being increasingly recognized. In this study, we found that miR-15b, an important miRNA during HBV infection and hepatocellular carcinoma development, directly binds hepatocyte nuclear factor 1α (HNF1α) mRNA, a negative regulator of HBV Enhancer I, to attenuate HNF1α expression, resulting in transactivation of HBV Enhancer I, in turn causing the enhancement of HBV replication and expression of HBV antigens, including HBx protein, finally leading to the down-regulated expression of miR-15b in both cell lines and mice in a long cascade of events. Our research showed that miR-15b promotes HBV replication by augmenting HBV Enhancer I activity via direct targeting HNF1α, while HBV replication and antigens expression, particularly the HBx protein, then repress the expression of miR-15b. The reciprocal regulation between miR-15b and HBV controls the level of HBV replication and might play a role in persistent HBV infection. This work adds to the body of knowledge concerning the complex interactions between HBV and host miRNAs.
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Xiaopeng
X
Dai
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Wei
W
Zhang
Henan Key Laboratory of Tumor Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450052, China.
Hongfei
H
Zhang
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Shihui
S
Sun
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Hong
H
Yu
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Yan
Y
Guo
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Zhihua
Z
Kou
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Guangyu
G
Zhao
Laboratory of Viral immunology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA.
Lanying
L
Du
Laboratory of Viral immunology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA.
Shibo
S
Jiang
Henan Key Laboratory of Tumor Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450052, China Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79968, USA.
Jianying
J
Zhang
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China yszhou@bmi.ac.cn.
Junfeng
J
Li
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China yszhou@bmi.ac.cn.
Yusen
Y
Zhou
D020413:3' Untranslated Regions; D000818:Animals; D045744:Cell Line, Tumor; D004742:Enhancer Elements, Genetic; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014779:Virus Replication
D020413:3' Untranslated Regions; D051538:Hepatocyte Nuclear Factor 1-alpha; C505361:MIRN15 microRNA, human; D035683:MicroRNAs