Cargando…

MicroRNA‐194 protects against chronic hepatitis B‐related liver damage by promoting hepatocyte growth via ACVR2B

Persistent infection with the hepatitis B virus leads to liver cirrhosis and hepatocellular carcinoma. MicroRNAs (miRNAs) play an important role in a variety of biological processes; however, the role of miRNAs in chronic hepatitis B (CHB)‐induced liver damage remains poorly understood. Here, we inv...

Descripción completa

Detalles Bibliográficos
Autores principales: Gao, Xue, Zhao, Pan, Hu, Jie, Zhu, Hongguang, Zhang, Jiming, Zhou, Zhongwen, Zhao, Jingmin, Tang, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111826/
https://www.ncbi.nlm.nih.gov/pubmed/30044042
http://dx.doi.org/10.1111/jcmm.13714
_version_ 1783350740194951168
author Gao, Xue
Zhao, Pan
Hu, Jie
Zhu, Hongguang
Zhang, Jiming
Zhou, Zhongwen
Zhao, Jingmin
Tang, Feng
author_facet Gao, Xue
Zhao, Pan
Hu, Jie
Zhu, Hongguang
Zhang, Jiming
Zhou, Zhongwen
Zhao, Jingmin
Tang, Feng
author_sort Gao, Xue
collection PubMed
description Persistent infection with the hepatitis B virus leads to liver cirrhosis and hepatocellular carcinoma. MicroRNAs (miRNAs) play an important role in a variety of biological processes; however, the role of miRNAs in chronic hepatitis B (CHB)‐induced liver damage remains poorly understood. Here, we investigated the role of miRNAs in CHB‐related liver damage. Microarray analysis of the expression of miRNAs in 22 CHB patients and 33 healthy individuals identified miR‐194 as one of six differentially expressed miRNAs. miR‐194 was up‐regulated in correlation with increased liver damage in the plasma or liver tissues of CHB patients. In mice subjected to 2/3 partial hepatectomy, miR‐194 was up‐regulated in liver tissues in correlation with hepatocyte growth and in parallel with the down‐regulation of the activin receptor ACVR2B. Overexpression of miR‐194 in human liver HL7702 cells down‐regulated ACVR2B mRNA and protein expression, promoted cell proliferation, acceleratedG1 to S cell cycle transition, and inhibited apoptosis, whereas knockdown of miR‐194 had the opposite effects. Luciferase reporter assays confirmed that ACVR2B is a direct target of miR‐194, and overexpression of ACVR2B significantly repressed cell proliferation and G1 to S phase transition and induced cell apoptosis. ACVR2B overexpression abolished the effect of miR‐194, indicating that miR‐194 promotes hepatocyte proliferation and inhibits apoptosis by down‐regulating ACVR2B. Taken together, these results indicate that miR‐194 plays a crucial role in hepatocyte proliferation and liver regeneration by targeting ACVR2B and may represent a novel therapeutic target for the treatment of CHB‐related liver damage.
format Online
Article
Text
id pubmed-6111826
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-61118262018-09-01 MicroRNA‐194 protects against chronic hepatitis B‐related liver damage by promoting hepatocyte growth via ACVR2B Gao, Xue Zhao, Pan Hu, Jie Zhu, Hongguang Zhang, Jiming Zhou, Zhongwen Zhao, Jingmin Tang, Feng J Cell Mol Med Original Articles Persistent infection with the hepatitis B virus leads to liver cirrhosis and hepatocellular carcinoma. MicroRNAs (miRNAs) play an important role in a variety of biological processes; however, the role of miRNAs in chronic hepatitis B (CHB)‐induced liver damage remains poorly understood. Here, we investigated the role of miRNAs in CHB‐related liver damage. Microarray analysis of the expression of miRNAs in 22 CHB patients and 33 healthy individuals identified miR‐194 as one of six differentially expressed miRNAs. miR‐194 was up‐regulated in correlation with increased liver damage in the plasma or liver tissues of CHB patients. In mice subjected to 2/3 partial hepatectomy, miR‐194 was up‐regulated in liver tissues in correlation with hepatocyte growth and in parallel with the down‐regulation of the activin receptor ACVR2B. Overexpression of miR‐194 in human liver HL7702 cells down‐regulated ACVR2B mRNA and protein expression, promoted cell proliferation, acceleratedG1 to S cell cycle transition, and inhibited apoptosis, whereas knockdown of miR‐194 had the opposite effects. Luciferase reporter assays confirmed that ACVR2B is a direct target of miR‐194, and overexpression of ACVR2B significantly repressed cell proliferation and G1 to S phase transition and induced cell apoptosis. ACVR2B overexpression abolished the effect of miR‐194, indicating that miR‐194 promotes hepatocyte proliferation and inhibits apoptosis by down‐regulating ACVR2B. Taken together, these results indicate that miR‐194 plays a crucial role in hepatocyte proliferation and liver regeneration by targeting ACVR2B and may represent a novel therapeutic target for the treatment of CHB‐related liver damage. John Wiley and Sons Inc. 2018-07-25 2018-09 /pmc/articles/PMC6111826/ /pubmed/30044042 http://dx.doi.org/10.1111/jcmm.13714 Text en © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Gao, Xue
Zhao, Pan
Hu, Jie
Zhu, Hongguang
Zhang, Jiming
Zhou, Zhongwen
Zhao, Jingmin
Tang, Feng
MicroRNA‐194 protects against chronic hepatitis B‐related liver damage by promoting hepatocyte growth via ACVR2B
title MicroRNA‐194 protects against chronic hepatitis B‐related liver damage by promoting hepatocyte growth via ACVR2B
title_full MicroRNA‐194 protects against chronic hepatitis B‐related liver damage by promoting hepatocyte growth via ACVR2B
title_fullStr MicroRNA‐194 protects against chronic hepatitis B‐related liver damage by promoting hepatocyte growth via ACVR2B
title_full_unstemmed MicroRNA‐194 protects against chronic hepatitis B‐related liver damage by promoting hepatocyte growth via ACVR2B
title_short MicroRNA‐194 protects against chronic hepatitis B‐related liver damage by promoting hepatocyte growth via ACVR2B
title_sort microrna‐194 protects against chronic hepatitis b‐related liver damage by promoting hepatocyte growth via acvr2b
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111826/
https://www.ncbi.nlm.nih.gov/pubmed/30044042
http://dx.doi.org/10.1111/jcmm.13714
work_keys_str_mv AT gaoxue microrna194protectsagainstchronichepatitisbrelatedliverdamagebypromotinghepatocytegrowthviaacvr2b
AT zhaopan microrna194protectsagainstchronichepatitisbrelatedliverdamagebypromotinghepatocytegrowthviaacvr2b
AT hujie microrna194protectsagainstchronichepatitisbrelatedliverdamagebypromotinghepatocytegrowthviaacvr2b
AT zhuhongguang microrna194protectsagainstchronichepatitisbrelatedliverdamagebypromotinghepatocytegrowthviaacvr2b
AT zhangjiming microrna194protectsagainstchronichepatitisbrelatedliverdamagebypromotinghepatocytegrowthviaacvr2b
AT zhouzhongwen microrna194protectsagainstchronichepatitisbrelatedliverdamagebypromotinghepatocytegrowthviaacvr2b
AT zhaojingmin microrna194protectsagainstchronichepatitisbrelatedliverdamagebypromotinghepatocytegrowthviaacvr2b
AT tangfeng microrna194protectsagainstchronichepatitisbrelatedliverdamagebypromotinghepatocytegrowthviaacvr2b