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

Abstract

PurposeHistone 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 designHDAC5 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.ResultsHDAC5 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.ConclusionsOur 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.

Histone Deacetylase Inhibitors: An Attractive Therapeutic Strategy Against Breast Cancer

“…HDAC inhibitors have a potent role in cancer pathogenesis and progression. A number of reports indicate that in certain types of cancer, HDAC levels are increased (21)(22)(23)(24).…”

Histone Deacetylases as New Therapeutic Targets in Triple-negative Breast Cancer: Progress and Promises

“…It is clear that both histone acetylation and deacetylation affect chromatin remodeling as strong epigenetic mechanisms. Interestingly, evidence from several reports indicates that HDAC levels are increased in certain cancer types (22)(23)(24). In addition, HDAC inhibitors have been reported to enhance the acetylation of histones, in tumor cells (25).…”

Effect of BCLAF1 on HDAC inhibitor LMK-235-mediated apoptosis of diffuse large B cell lymphoma cells and its mechanism

“…By contrast, specific HDACi is well-tolerated, and LMK-235 is a novel HDACi with HDAC isoform selectivity that is a specific inhibitor of HDAC4 and HDAC5. 15,16 In addition, previous reports have investigated the effects of vadarnota (SAHA) on diffuse large B-cell lymphoma, 17,18 however, there is currently no study on the effect of specific HDACi LMK-235 on DLBCL.…”