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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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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 |
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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 |
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