Aging
Navigate
Submit an Article
Research Paper|Volume 8, Issue 6|pp 1236—1248

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

Li-Si Zeng1,2,3, Xian-Zi Yang1,2,3, Yue-Feng Wen4, Shi-Juan Mai1,2,3, Meng-He Wang1,2,3, Mei-Yin Zhang1,2,3, X.F. Steven Zheng1,5, Hui-Yun Wang1,2,3
  • 1State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
  • 2Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
  • 3Guangdong Esophageal Cancer Institute, Guangzhou, 510060, China
  • 4Cancer Center of Guangzhou Medical University, Guangzhou, 510095, China
  • 5Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ 08901, USA

* * Equal contribution

Received: April 27, 2016Accepted: May 30, 2016Published: June 13, 2016
https://doi.org/10.18632/aging.100980

Copyright: © 2016 Zeng et al. 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.

Abstract

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.