Oncotarget

Research Papers:

This article has been corrected. Correction in: Oncotarget. 2017; 8:30619-20.

HDAC5, a potential therapeutic target and prognostic biomarker, promotes proliferation, invasion and migration in human breast cancer

Anqi Li, Zebing Liu, Ming Li, Shuling Zhou, Yan Xu, Yaoxing Xiao and Wentao Yang _

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Oncotarget. 2016; 7:37966-37978. https://doi.org/10.18632/oncotarget.9274

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Abstract

Anqi Li1,*, Zebing Liu2,*, Ming Li1,*, Shuling Zhou1, Yan Xu1, Yaoxing Xiao1, Wentao Yang1

1Department of Pathology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China

2Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, P.R. China

*These authors have contributed equally to this work

Correspondence to:

Wentao Yang, email: [email protected]

Keywords: histone deacetylase, breast cancer, HDAC inhibitor, proteasome inhibitor, drug target

Received: September 23, 2015    Accepted: April 26, 2016    Published: May 10, 2016

ABSTRACT

Purpose: Histone deacetylase 5 (HDAC5) is an important protein in neural and cardiac diseases and a potential drug target. However, little is known regarding the specific role of HDAC5 in breast cancer (BC). We aimed to evaluate HDAC5 expression in human breast tumors and to determine the effects of the inhibition of HDAC5 expression in BC cells.

Experimental design: HDAC5 expression was evaluated in BC patients and was correlated with clinical features and with patient prognosis. Functional experiments were performed using shRNA and the selective HDAC inhibitor LMK-235 for HDAC5 knockdown and inhibition in BC cells. The synergistic effects of LMK-235 with the proteasome inhibitor bortezomib were also examined.

Results: HDAC5 was extensively expressed in human BC tissues, and high HDAC5 expression was associated with an inferior prognosis. Knockdown of HDAC5 inhibited cell proliferation, migration, invasion, and enhanced apoptosis. The HDAC5 inhibitor LMK-235 inhibited cell growth and induced apoptosis, while the inclusion of bortezomib synergistically enhanced the efficacy of LMK-235.

Conclusions: Our findings indicate that HDAC5 is a promising prognostic marker and drug target for BC and that the combination of LMK-235 and bortezomib presents a novel therapeutic strategy for BC.


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