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Overexpressed HDAC4 is associated with poor survival and promotes tumor progression in esophageal carcinoma

Histone deacetylases (HDACs) mediate histone deacetylation, leading to transcriptional repression, which is involved in many diseases, including age-related tissue degeneration, heart failure and cancer. In this study, we were aimed to investigate the expression, clinical significance and biological...

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Autores principales: Zeng, Li-Si, Yang, Xian-Zi, Wen, Yue-Feng, Mai, Shi-Juan, Wang, Meng-He, Zhang, Mei-Yin, Zheng, X.F. Steven, Wang, Hui-Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931829/
https://www.ncbi.nlm.nih.gov/pubmed/27295551
http://dx.doi.org/10.18632/aging.100980
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author Zeng, Li-Si
Yang, Xian-Zi
Wen, Yue-Feng
Mai, Shi-Juan
Wang, Meng-He
Zhang, Mei-Yin
Zheng, X.F. Steven
Wang, Hui-Yun
author_facet Zeng, Li-Si
Yang, Xian-Zi
Wen, Yue-Feng
Mai, Shi-Juan
Wang, Meng-He
Zhang, Mei-Yin
Zheng, X.F. Steven
Wang, Hui-Yun
author_sort Zeng, Li-Si
collection PubMed
description Histone deacetylases (HDACs) mediate histone deacetylation, leading to transcriptional repression, which is involved in many diseases, including age-related tissue degeneration, heart failure and cancer. In this study, we were aimed to investigate the expression, clinical significance and biological function of HDAC4 in esophageal carcinoma (EC). We found that HDAC4 mRNA and protein are overexpressed in esophageal squamous cell carcinoma (ESCC) tissues and cell lines. HDAC4 overexpression is associated with higher tumor grade, advanced clinical stage and poor survival. Mechanistically, HDAC4 promotes proliferation and G1/S cell cycle progression in EC cells by inhibiting cyclin-dependent kinase (CDK) inhibitors p21 and p27 and up-regulating CDK2/4 and CDK-dependent Rb phosphorylation. HDAC4 also enhances ESCC cell migration. Furthermore, HDAC4 positively regulates epithelial-mesenchymal transition (EMT) by increasing the expression of Vimentin and decreasing the expression of E-Cadherin/α-Catenin. Together, our study shows that HDAC4 overexpression is important for the oncogenesis of EC, which may serve as a useful prognostic biomarker and therapeutic target for this malignancy.
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spelling pubmed-49318292016-07-18 Overexpressed HDAC4 is associated with poor survival and promotes tumor progression in esophageal carcinoma Zeng, Li-Si Yang, Xian-Zi Wen, Yue-Feng Mai, Shi-Juan Wang, Meng-He Zhang, Mei-Yin Zheng, X.F. Steven Wang, Hui-Yun Aging (Albany NY) Research Paper Histone deacetylases (HDACs) mediate histone deacetylation, leading to transcriptional repression, which is involved in many diseases, including age-related tissue degeneration, heart failure and cancer. In this study, we were aimed to investigate the expression, clinical significance and biological function of HDAC4 in esophageal carcinoma (EC). We found that HDAC4 mRNA and protein are overexpressed in esophageal squamous cell carcinoma (ESCC) tissues and cell lines. HDAC4 overexpression is associated with higher tumor grade, advanced clinical stage and poor survival. Mechanistically, HDAC4 promotes proliferation and G1/S cell cycle progression in EC cells by inhibiting cyclin-dependent kinase (CDK) inhibitors p21 and p27 and up-regulating CDK2/4 and CDK-dependent Rb phosphorylation. HDAC4 also enhances ESCC cell migration. Furthermore, HDAC4 positively regulates epithelial-mesenchymal transition (EMT) by increasing the expression of Vimentin and decreasing the expression of E-Cadherin/α-Catenin. Together, our study shows that HDAC4 overexpression is important for the oncogenesis of EC, which may serve as a useful prognostic biomarker and therapeutic target for this malignancy. Impact Journals LLC 2016-06-13 /pmc/articles/PMC4931829/ /pubmed/27295551 http://dx.doi.org/10.18632/aging.100980 Text en Copyright: © 2016 Zeng 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
Zeng, Li-Si
Yang, Xian-Zi
Wen, Yue-Feng
Mai, Shi-Juan
Wang, Meng-He
Zhang, Mei-Yin
Zheng, X.F. Steven
Wang, Hui-Yun
Overexpressed HDAC4 is associated with poor survival and promotes tumor progression in esophageal carcinoma
title Overexpressed HDAC4 is associated with poor survival and promotes tumor progression in esophageal carcinoma
title_full Overexpressed HDAC4 is associated with poor survival and promotes tumor progression in esophageal carcinoma
title_fullStr Overexpressed HDAC4 is associated with poor survival and promotes tumor progression in esophageal carcinoma
title_full_unstemmed Overexpressed HDAC4 is associated with poor survival and promotes tumor progression in esophageal carcinoma
title_short Overexpressed HDAC4 is associated with poor survival and promotes tumor progression in esophageal carcinoma
title_sort overexpressed hdac4 is associated with poor survival and promotes tumor progression in esophageal carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931829/
https://www.ncbi.nlm.nih.gov/pubmed/27295551
http://dx.doi.org/10.18632/aging.100980
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