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He, JC; Yao, W; Wang, JM; Schemmer, P; Yang, Y; Liu, Y; Qian, YW; Qi, WP; Zhang, J; Shen, Q; Yang, T.
TACC3 overexpression in cholangiocarcinoma correlates with poor prognosis and is a potential anti-cancer molecular drug target for HDAC inhibitors.
Oncotarget. 2016; 7(46):75441-75456 Doi: 10.18632/oncotarget.12254 [OPEN ACCESS]
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Co-Autor*innen der Med Uni Graz
Schemmer Peter
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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.
Find related publications in this database (using NLM MeSH Indexing)
Adult -
Aged -
Animals -
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Cell Line, Tumor -
Cell Movement - genetics
Cell Proliferation - genetics
Cholangiocarcinoma - drug therapy
Cholangiocarcinoma - genetics
Cholangiocarcinoma - mortality
Cholangiocarcinoma - pathology
Disease Models, Animal -
Female -
Gene Expression -
Gene Expression Profiling -
Gene Knockdown Techniques -
Histone Deacetylase 2 - genetics
Histone Deacetylase 2 - metabolism
Histone Deacetylase Inhibitors - pharmacology
Histone Deacetylase Inhibitors - therapeutic use
Histone Deacetylases - genetics
Histone Deacetylases - metabolism
Humans -
Male -
Mice -
Microtubule-Associated Proteins - antagonists & inhibitors
Microtubule-Associated Proteins - genetics
Middle Aged -
Molecular Targeted Therapy -
Neoplasm Grading -
Neoplasm Metastasis -
Neoplasm Staging -
Prognosis -
Proportional Hazards Models -
Xenograft Model Antitumor Assays -

Find related publications in this database (Keywords)
histone deacetylase (HDAC)
HDAC inhibitors (HDACIs)
microarray
transforming acidic coiled-coil-containing protein 3 (TACC3)
cholangiocarcinoma (CCA)
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