Oncotarget

Research Papers:

Down-regulation of HDAC3 inhibits growth of cholangiocarcinoma by inducing apoptosis

Mingming Zhang, Yuyao Yin, Robert G. Dorfman, Tianhui Zou, Yida Pan, Yang Li, Yuming Wang, Qian Zhou, Lixing Zhou, Bo Kong, Helmut Friess, Jun Zhang, Shimin Zhao, Lei Wang _ and Xiaoping Zou

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Oncotarget. 2017; 8:99402-99413. https://doi.org/10.18632/oncotarget.19660

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Abstract

Mingming Zhang1,2,*, Yuyao Yin1,*, Robert G. Dorfman5, Tianhui Zou6, Yida Pan3, Yang Li1, Yuming Wang1, Qian Zhou4, Lixing Zhou1, Bo Kong1,7, Helmut Friess7, Jun Zhang3, Shimin Zhao2,3,4, Lei Wang1 and Xiaoping Zou1

1Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, China

2Key Laboratory of Reproduction Regulation of NPFPC (SIPPR, IRD), Shanghai, China

3Department of Digestive Diseases of Huashan Hospital, Shanghai, China

4School of Life Sciences, Fudan University, Shanghai, China

5Northwestern University Feinberg School of Medicine, Chicago, IL, USA

6Department of Gastroenterology, Renji Hospital, Shanghai Jiaotong University, Shanghai, China

7Department of Surgery, Technical University of Munich (TUM), Munich, Germany

*These authors have contributed equally to this work

Correspondence to:

Lei Wang, email: [email protected]

Xiaoping Zou, email: [email protected]

Keywords: apoptosis, cholangiocarcinoma, HDAC3, prognosis

Received: March 02, 2017    Accepted: May 21, 2017    Published: July 28, 2017

ABSTRACT

Class I histone deacetylases (HDACs) inhibit expression of tumor suppressor genes by removing acetyl groups from histone lysine residues, thereby increasing cancer cell survival and proliferation. We evaluated the expression of class I HDACs in cholangiocarcinoma (CCA). HDAC3 expression was specifically increased in CCA tissues and correlated with reduced patient survival. HDAC3 overexpression inhibited apoptosis and promoted CCA cell proliferation. Conversely, HDAC3 knockdown or pharmacological inhibition decreased CCA cell growth and increased caspase-dependent apoptosis. Inhibition of class I HDACs blocked HDAC3-catalyzed deacetylation and increased expression of downstream pro-apoptotic targets in vitro and in vivo. These results demonstrate for the first time that down-regulation of HDAC3 induces apoptosis in human CCA cells, indicating that inhibiting HDAC3 may be an effective therapeutic strategy for treating CCA.


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