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RASSF10 is an epigenetically inactivated tumor suppressor and independent prognostic factor in hepatocellular carcinoma
Methylation of the Ras-association domain family 10 (RASSF10) promoter region correlates with clinicopathological characteristics and poor prognosis in several human cancers. Here, we examined RASSF10 expression in hepatocellular carcinoma (HCC) and its role in hepatocarcinogenesis. RASSF10 mRNA and...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826205/ https://www.ncbi.nlm.nih.gov/pubmed/26701853 http://dx.doi.org/10.18632/oncotarget.6654 |
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author | Wang, Fei Feng, Ying Li, Peng Wang, Kun Feng, Liang Liu, Yi-Fei Huang, Hua Guo, Yi-Bing Mao, Qin-Sheng Xue, Wan-Jiang |
author_facet | Wang, Fei Feng, Ying Li, Peng Wang, Kun Feng, Liang Liu, Yi-Fei Huang, Hua Guo, Yi-Bing Mao, Qin-Sheng Xue, Wan-Jiang |
author_sort | Wang, Fei |
collection | PubMed |
description | Methylation of the Ras-association domain family 10 (RASSF10) promoter region correlates with clinicopathological characteristics and poor prognosis in several human cancers. Here, we examined RASSF10 expression in hepatocellular carcinoma (HCC) and its role in hepatocarcinogenesis. RASSF10 mRNA and protein levels were downregulated in both HCC cell lines and patient tissue samples. In patient tissues, low RASSF10 levels correlated with hepatocirrhosis, poor tumor differentiation, tumor thrombus and Barcelona Clinic Liver Cancer stage, and were indicative of increased tumor recurrence and reduced patient survival. Low RASSF10 expression was associated with promoter hypermethylation, which was in turn associated with polycyclic aromatic hydrocarbon and aflatoxin B1 exposure, but not DNA methyltransferase expression. Overexpression of RASSF10 in HCC cell lines suppressed cell growth and colony formation, and induced apoptosis by up- or down-regulating specific Bcl-2 family proteins. RASSF10 overexpression increased pro-apoptotic Bax and Bad levels, but decreased anti-apoptotic Bcl-2 and Bcl-xl expression. Overexpression also inhibited tumor formation in nude mice and reduced cell migration and invasion by inhibiting the epithelial-mesenchymal transition. RASSF10 knockdown promoted cell growth. Our results show that RASSF10 is frequently hypermethylated and down-regulated in HCC and can potentially serve as a useful biomarker predictive of HCC patient prognosis. |
format | Online Article Text |
id | pubmed-4826205 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-48262052016-05-09 RASSF10 is an epigenetically inactivated tumor suppressor and independent prognostic factor in hepatocellular carcinoma Wang, Fei Feng, Ying Li, Peng Wang, Kun Feng, Liang Liu, Yi-Fei Huang, Hua Guo, Yi-Bing Mao, Qin-Sheng Xue, Wan-Jiang Oncotarget Research Paper Methylation of the Ras-association domain family 10 (RASSF10) promoter region correlates with clinicopathological characteristics and poor prognosis in several human cancers. Here, we examined RASSF10 expression in hepatocellular carcinoma (HCC) and its role in hepatocarcinogenesis. RASSF10 mRNA and protein levels were downregulated in both HCC cell lines and patient tissue samples. In patient tissues, low RASSF10 levels correlated with hepatocirrhosis, poor tumor differentiation, tumor thrombus and Barcelona Clinic Liver Cancer stage, and were indicative of increased tumor recurrence and reduced patient survival. Low RASSF10 expression was associated with promoter hypermethylation, which was in turn associated with polycyclic aromatic hydrocarbon and aflatoxin B1 exposure, but not DNA methyltransferase expression. Overexpression of RASSF10 in HCC cell lines suppressed cell growth and colony formation, and induced apoptosis by up- or down-regulating specific Bcl-2 family proteins. RASSF10 overexpression increased pro-apoptotic Bax and Bad levels, but decreased anti-apoptotic Bcl-2 and Bcl-xl expression. Overexpression also inhibited tumor formation in nude mice and reduced cell migration and invasion by inhibiting the epithelial-mesenchymal transition. RASSF10 knockdown promoted cell growth. Our results show that RASSF10 is frequently hypermethylated and down-regulated in HCC and can potentially serve as a useful biomarker predictive of HCC patient prognosis. Impact Journals LLC 2015-12-18 /pmc/articles/PMC4826205/ /pubmed/26701853 http://dx.doi.org/10.18632/oncotarget.6654 Text en Copyright: © 2016 Wang 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 Wang, Fei Feng, Ying Li, Peng Wang, Kun Feng, Liang Liu, Yi-Fei Huang, Hua Guo, Yi-Bing Mao, Qin-Sheng Xue, Wan-Jiang RASSF10 is an epigenetically inactivated tumor suppressor and independent prognostic factor in hepatocellular carcinoma |
title | RASSF10 is an epigenetically inactivated tumor suppressor and independent prognostic factor in hepatocellular carcinoma |
title_full | RASSF10 is an epigenetically inactivated tumor suppressor and independent prognostic factor in hepatocellular carcinoma |
title_fullStr | RASSF10 is an epigenetically inactivated tumor suppressor and independent prognostic factor in hepatocellular carcinoma |
title_full_unstemmed | RASSF10 is an epigenetically inactivated tumor suppressor and independent prognostic factor in hepatocellular carcinoma |
title_short | RASSF10 is an epigenetically inactivated tumor suppressor and independent prognostic factor in hepatocellular carcinoma |
title_sort | rassf10 is an epigenetically inactivated tumor suppressor and independent prognostic factor in hepatocellular carcinoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826205/ https://www.ncbi.nlm.nih.gov/pubmed/26701853 http://dx.doi.org/10.18632/oncotarget.6654 |
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