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

نویسندگان

  • Anqi Li
  • Zebing Liu
  • Ming Li
  • Shuling Zhou
  • Yan Xu
  • Yaoxing Xiao
  • Wentao Yang
چکیده

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.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

MiR-493 suppresses the proliferation and invasion of gastric cancer cells by targeting RhoC

Objective(s):MiRNAs have been proposed to be key regulators of tumorigenesis, progression and metastasis. However, their effect and prognostic value in gastric cancer is still poorly known. Materials and Methods: Gastric cancer cell lines were cultured. Tissue samples obtained from 36 gastric cancer patients were used for quantitative real-time PCR (qRT-PCR) analysis. The tissue microarrays (T...

متن کامل

MiR-6165 Dysregulation in Breast Cancer and Its Effect on Cell Proliferation and Migration

Background: ncRNAs have been identified as oncogenic drivers and tumor suppressors in any type of cancer. Although many classes of ncRNAs have been reported, most studies have been performed on microRNAs (miRNAs). miRNAs can regulate several target genes and affect important processes such as homeostasis, angiogenesis, cell proliferation, differentiation, and apoptosis. Located in the p75NTR ge...

متن کامل

miR-92a promotes hepatocellular carcinoma cells proliferation and invasion by FOXA2 targeting

Objective(s): MicroRNAs (miRNAs) are considered as powerful, post-transcriptional regulators of gene expression in hepatocellular carcinoma cells (HCC). However, the function of miR-92a is still unclear in HCC. Materials and Methods: Expression of miR-92a in human HCC cell lines was evaluated using qRT-PCR. MTT assay and transwell assay were used to examine the function of miR-92a in HepG2 and ...

متن کامل

LncRNA Miat Promotes Proliferation of Cervical Cancer Cells and Acts as an Anti-apoptotic Factor

There are a sub-population of cells in tumor tissues known as cancer stem cells (CSCs) which have similar features with stem cells, including self-renewal and differentiation capacity. Recently, it was established that not only stem cells factors such as Oct4, but also ES-associated lncRNAs are contributing to various regulatory aspects of CSCs. Myocardial infarction associated transcript (MIAT...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2016