Modulation of HBV replication by microRNA-15b through targeting hepatocyte nuclear factor 1α.

Abstract:

: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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Dai X,Zhang W,Zhang H,Sun S,Yu H,Guo Y,Kou Z,Zhao G,Du L,Jiang S,Zhang J,Li J,Zhou Y

doi

10.1093/nar/gku260

subject

Has Abstract

pub_date

2014-06-01 00:00:00

pages

6578-90

issue

10

eissn

0305-1048

issn

1362-4962

pii

gku260

journal_volume

42

pub_type

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