Cargando…
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 developme...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041434/ https://www.ncbi.nlm.nih.gov/pubmed/24705650 http://dx.doi.org/10.1093/nar/gku260 |
_version_ | 1782318675812941824 |
---|---|
author | Dai, Xiaopeng Zhang, Wei Zhang, Hongfei Sun, Shihui Yu, Hong Guo, Yan Kou, Zhihua Zhao, Guangyu Du, Lanying Jiang, Shibo Zhang, Jianying Li, Junfeng Zhou, Yusen |
author_facet | Dai, Xiaopeng Zhang, Wei Zhang, Hongfei Sun, Shihui Yu, Hong Guo, Yan Kou, Zhihua Zhao, Guangyu Du, Lanying Jiang, Shibo Zhang, Jianying Li, Junfeng Zhou, Yusen |
author_sort | Dai, Xiaopeng |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4041434 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-40414342014-06-11 Modulation of HBV replication by microRNA-15b through targeting hepatocyte nuclear factor 1α Dai, Xiaopeng Zhang, Wei Zhang, Hongfei Sun, Shihui Yu, Hong Guo, Yan Kou, Zhihua Zhao, Guangyu Du, Lanying Jiang, Shibo Zhang, Jianying Li, Junfeng Zhou, Yusen Nucleic Acids Res RNA 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. Oxford University Press 2014-06-01 2014-04-04 /pmc/articles/PMC4041434/ /pubmed/24705650 http://dx.doi.org/10.1093/nar/gku260 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | RNA Dai, Xiaopeng Zhang, Wei Zhang, Hongfei Sun, Shihui Yu, Hong Guo, Yan Kou, Zhihua Zhao, Guangyu Du, Lanying Jiang, Shibo Zhang, Jianying Li, Junfeng Zhou, Yusen Modulation of HBV replication by microRNA-15b through targeting hepatocyte nuclear factor 1α |
title | Modulation of HBV replication by microRNA-15b through targeting hepatocyte nuclear factor 1α |
title_full | Modulation of HBV replication by microRNA-15b through targeting hepatocyte nuclear factor 1α |
title_fullStr | Modulation of HBV replication by microRNA-15b through targeting hepatocyte nuclear factor 1α |
title_full_unstemmed | Modulation of HBV replication by microRNA-15b through targeting hepatocyte nuclear factor 1α |
title_short | Modulation of HBV replication by microRNA-15b through targeting hepatocyte nuclear factor 1α |
title_sort | modulation of hbv replication by microrna-15b through targeting hepatocyte nuclear factor 1α |
topic | RNA |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041434/ https://www.ncbi.nlm.nih.gov/pubmed/24705650 http://dx.doi.org/10.1093/nar/gku260 |
work_keys_str_mv | AT daixiaopeng modulationofhbvreplicationbymicrorna15bthroughtargetinghepatocytenuclearfactor1a AT zhangwei modulationofhbvreplicationbymicrorna15bthroughtargetinghepatocytenuclearfactor1a AT zhanghongfei modulationofhbvreplicationbymicrorna15bthroughtargetinghepatocytenuclearfactor1a AT sunshihui modulationofhbvreplicationbymicrorna15bthroughtargetinghepatocytenuclearfactor1a AT yuhong modulationofhbvreplicationbymicrorna15bthroughtargetinghepatocytenuclearfactor1a AT guoyan modulationofhbvreplicationbymicrorna15bthroughtargetinghepatocytenuclearfactor1a AT kouzhihua modulationofhbvreplicationbymicrorna15bthroughtargetinghepatocytenuclearfactor1a AT zhaoguangyu modulationofhbvreplicationbymicrorna15bthroughtargetinghepatocytenuclearfactor1a AT dulanying modulationofhbvreplicationbymicrorna15bthroughtargetinghepatocytenuclearfactor1a AT jiangshibo modulationofhbvreplicationbymicrorna15bthroughtargetinghepatocytenuclearfactor1a AT zhangjianying modulationofhbvreplicationbymicrorna15bthroughtargetinghepatocytenuclearfactor1a AT lijunfeng modulationofhbvreplicationbymicrorna15bthroughtargetinghepatocytenuclearfactor1a AT zhouyusen modulationofhbvreplicationbymicrorna15bthroughtargetinghepatocytenuclearfactor1a |