Oncotarget

Research Papers:

TACC3 overexpression in cholangiocarcinoma correlates with poor prognosis and is a potential anti-cancer molecular drug target for HDAC inhibitors

Jun-chuang He, Wei Yao, Jian-ming Wang _, Peter Schemmer, Yan Yang, Yan Liu, Ya-wei Qian, Wei-peng Qi, Jian Zhang, Qi Shen and Tao Yang

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Oncotarget. 2016; 7:75441-75456. https://doi.org/10.18632/oncotarget.12254

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Abstract

Jun-chuang He1,*, Wei Yao1,*, Jian-ming Wang1, Peter Schemmer2, Yan Yang1, Yan Liu1, Ya-wei Qian1, Wei-peng Qi1, Jian Zhang1, Qi Shen1, Tao Yang1

1Department of Biliary and Pancreatic Surgery/Cancer Research Center Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China

2Department of General and Transplant Surgery, University Hospital Heidelberg, Heidelberg 69120, Germany

*These authors have contributed equally to this work

Correspondence to:

Jian-ming Wang, email: wjm18jgm@aliyun.com

Keywords: histone deacetylase (HDAC), HDAC inhibitors (HDACIs), microarray, transforming acidic coiled-coil-containing protein 3 (TACC3), cholangiocarcinoma (CCA)

Received: March 19, 2016    Accepted: September 13, 2016    Published: September 26, 2016

ABSTRACT

Histone deacetylases (HDACs) have been implicated in multiple malignant tumors, and HDAC inhibitors (HDACIs) exert anti-cancer effects. However, the expression of HDACs and the anti-tumor mechanism of HDACIs in cholangiocarcinoma (CCA) have not yet been elucidated. In this study, we found that expression of HDACs 2, 3, and 8 were up-regulated in CCA tissues and those patients with high expression of HDAC2 and/or HDAC3 had a worse prognosis. In CCA cells, two HDACIs, trichostatin (TSA) and vorinostat (SAHA), suppressed proliferation and induced apoptosis and G2/M cycle arrest. Microarray analysis revealed that TACC3 mRNA was down-regulated in CCA cells treated with TSA. TACC3 was highly expressed in CCA tissues and predicted a poor prognosis in CCA patients. TACC3 knockdown induced G2/M cycle arrest and suppressed the invasion, metastasis, and proliferation of CCA cells, both in vitro and in vivo. TACC3 overexpression reversed the effects of its knockdown. These findings suggest TACC3 may be a useful prognostic biomarker for CCA and is a potential therapeutic target for HDACIs.


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