Cargando…

Hepatitis B virus X protein amplifies TGF-β promotion on HCC motility through down-regulating PPM1a

Over-activation of transforming growth factor-β (TGF-β) signaling pathway promotes cell migration and invasion in hepatocellular carcinoma (HCC). The Hepatitis B virus X protein (HBx) is involved in the enhancement of TGF-β signaling pathway in HCC while the mechanism remains unclear. Protein phosph...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Yuan, Xu, Yong, Ma, Hongxin, Wang, Bo, Xu, Leiqi, Zhang, Hualin, Song, Xiaojia, Gao, Lifen, Liang, Xiaohong, Ma, Chunhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078080/
https://www.ncbi.nlm.nih.gov/pubmed/27121309
http://dx.doi.org/10.18632/oncotarget.8884
_version_ 1782462306548973568
author Liu, Yuan
Xu, Yong
Ma, Hongxin
Wang, Bo
Xu, Leiqi
Zhang, Hualin
Song, Xiaojia
Gao, Lifen
Liang, Xiaohong
Ma, Chunhong
author_facet Liu, Yuan
Xu, Yong
Ma, Hongxin
Wang, Bo
Xu, Leiqi
Zhang, Hualin
Song, Xiaojia
Gao, Lifen
Liang, Xiaohong
Ma, Chunhong
author_sort Liu, Yuan
collection PubMed
description Over-activation of transforming growth factor-β (TGF-β) signaling pathway promotes cell migration and invasion in hepatocellular carcinoma (HCC). The Hepatitis B virus X protein (HBx) is involved in the enhancement of TGF-β signaling pathway in HCC while the mechanism remains unclear. Protein phosphatase magnesium dependent 1A (PPM1a) functions as a phosphatase essential for terminating the TGF-β signaling pathway by dephosphorylating p-Smad2/3. In this study, we found that HBx dose-dependently downregulated PPM1a protein level in the presence of TGF-β, while having no effect on its mRNA level. Further study showed that HBx increased the ubiquitination of PPM1a and accelerated its proteasomal degradation. Restoration of PPM1a almost completely abrogated HBx mediated promotion on HCC migration and invasion. This involvement of PPM1a in HBx-related HCC was further confirmed with immunohistochemical analysis in HCC tissue. Compared with paired pericarcinous tissue, HCC tissue showed decreased PPM1a level. Besides, PPM1a level is negatively correlated with HBx expression. Taken together, our present study suggests that HBx-induced degradation of PPM1a is a novel mechanism for over-activation of TGF-β pathway in HCC development, which might provide potential candidates for clinical diagnosis and treatment.
format Online
Article
Text
id pubmed-5078080
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-50780802016-10-28 Hepatitis B virus X protein amplifies TGF-β promotion on HCC motility through down-regulating PPM1a Liu, Yuan Xu, Yong Ma, Hongxin Wang, Bo Xu, Leiqi Zhang, Hualin Song, Xiaojia Gao, Lifen Liang, Xiaohong Ma, Chunhong Oncotarget Research Paper Over-activation of transforming growth factor-β (TGF-β) signaling pathway promotes cell migration and invasion in hepatocellular carcinoma (HCC). The Hepatitis B virus X protein (HBx) is involved in the enhancement of TGF-β signaling pathway in HCC while the mechanism remains unclear. Protein phosphatase magnesium dependent 1A (PPM1a) functions as a phosphatase essential for terminating the TGF-β signaling pathway by dephosphorylating p-Smad2/3. In this study, we found that HBx dose-dependently downregulated PPM1a protein level in the presence of TGF-β, while having no effect on its mRNA level. Further study showed that HBx increased the ubiquitination of PPM1a and accelerated its proteasomal degradation. Restoration of PPM1a almost completely abrogated HBx mediated promotion on HCC migration and invasion. This involvement of PPM1a in HBx-related HCC was further confirmed with immunohistochemical analysis in HCC tissue. Compared with paired pericarcinous tissue, HCC tissue showed decreased PPM1a level. Besides, PPM1a level is negatively correlated with HBx expression. Taken together, our present study suggests that HBx-induced degradation of PPM1a is a novel mechanism for over-activation of TGF-β pathway in HCC development, which might provide potential candidates for clinical diagnosis and treatment. Impact Journals LLC 2016-04-21 /pmc/articles/PMC5078080/ /pubmed/27121309 http://dx.doi.org/10.18632/oncotarget.8884 Text en Copyright: © 2016 Liu et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Liu, Yuan
Xu, Yong
Ma, Hongxin
Wang, Bo
Xu, Leiqi
Zhang, Hualin
Song, Xiaojia
Gao, Lifen
Liang, Xiaohong
Ma, Chunhong
Hepatitis B virus X protein amplifies TGF-β promotion on HCC motility through down-regulating PPM1a
title Hepatitis B virus X protein amplifies TGF-β promotion on HCC motility through down-regulating PPM1a
title_full Hepatitis B virus X protein amplifies TGF-β promotion on HCC motility through down-regulating PPM1a
title_fullStr Hepatitis B virus X protein amplifies TGF-β promotion on HCC motility through down-regulating PPM1a
title_full_unstemmed Hepatitis B virus X protein amplifies TGF-β promotion on HCC motility through down-regulating PPM1a
title_short Hepatitis B virus X protein amplifies TGF-β promotion on HCC motility through down-regulating PPM1a
title_sort hepatitis b virus x protein amplifies tgf-β promotion on hcc motility through down-regulating ppm1a
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078080/
https://www.ncbi.nlm.nih.gov/pubmed/27121309
http://dx.doi.org/10.18632/oncotarget.8884
work_keys_str_mv AT liuyuan hepatitisbvirusxproteinamplifiestgfbpromotiononhccmotilitythroughdownregulatingppm1a
AT xuyong hepatitisbvirusxproteinamplifiestgfbpromotiononhccmotilitythroughdownregulatingppm1a
AT mahongxin hepatitisbvirusxproteinamplifiestgfbpromotiononhccmotilitythroughdownregulatingppm1a
AT wangbo hepatitisbvirusxproteinamplifiestgfbpromotiononhccmotilitythroughdownregulatingppm1a
AT xuleiqi hepatitisbvirusxproteinamplifiestgfbpromotiononhccmotilitythroughdownregulatingppm1a
AT zhanghualin hepatitisbvirusxproteinamplifiestgfbpromotiononhccmotilitythroughdownregulatingppm1a
AT songxiaojia hepatitisbvirusxproteinamplifiestgfbpromotiononhccmotilitythroughdownregulatingppm1a
AT gaolifen hepatitisbvirusxproteinamplifiestgfbpromotiononhccmotilitythroughdownregulatingppm1a
AT liangxiaohong hepatitisbvirusxproteinamplifiestgfbpromotiononhccmotilitythroughdownregulatingppm1a
AT machunhong hepatitisbvirusxproteinamplifiestgfbpromotiononhccmotilitythroughdownregulatingppm1a