Inhibition of BRD4 Suppresses Cell Proliferation and Induces Apoptosis in Renal Cell Carcinoma
Background/Aims: Renal cell carcinoma (RCC) remains an intractable genitourinary malignancy. Resistance to chemotherapy or targeted therapies in RCC is presumably due to the complicated underlying molecular mechanisms and insufficient understanding. The aim of this research was to assess the express...
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Cell Physiol Biochem Press GmbH & Co KG
2017-04-01
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doaj-667c64d4e84a421b968cc410f8ff002f2020-11-25T01:27:46ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782017-04-014151947195610.1159/000472407472407Inhibition of BRD4 Suppresses Cell Proliferation and Induces Apoptosis in Renal Cell CarcinomaXinchao WuDong LiuXuemei GaoFei XieDan TaoXingyuan XiaoLiang WangGuosong JiangFuqing ZengBackground/Aims: Renal cell carcinoma (RCC) remains an intractable genitourinary malignancy. Resistance to chemotherapy or targeted therapies in RCC is presumably due to the complicated underlying molecular mechanisms and insufficient understanding. The aim of this research was to assess the expression and role of bromodomain-4 protein (BRD4) in RCC and evaluate the effects of BRD4 inhibitor JQ1 for RCC treatment. Methods: BRD4 expressionlevels were assessed by qRT-PCR and western blot in RCC tissues and cells. The effects of BRD4 knockdown or JQ1 on RCC cells were assessed by MTT assay and flow cytometry. The effects of in vivo treatment were evaluated through xenograft experiments. Results: BRD4 is significantly overexpressed in RCC, and is related to tumor stage and lymph node metastasis. Inhibition of BRD4 suppressed RCC cell proliferation, induced cell apoptosis in vitro and repressed tumor growth in vivo. Inhibition of BRD4 decreased BCL2 and C-MYC expression while increased BAX and cleaved caspase3 expression, and strikingly diminished the recruitment of BRD4 to BCL2 promoter. Conclusions: Our research reveals that BRD4 probably play a critical role in RCC progression, and is a new promising target for pharmacological treatment directed against this intractable disease.http://www.karger.com/Article/FullText/472407Renal cell carcinomaBRD4JQ1ApoptosisCell proliferation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xinchao Wu Dong Liu Xuemei Gao Fei Xie Dan Tao Xingyuan Xiao Liang Wang Guosong Jiang Fuqing Zeng |
spellingShingle |
Xinchao Wu Dong Liu Xuemei Gao Fei Xie Dan Tao Xingyuan Xiao Liang Wang Guosong Jiang Fuqing Zeng Inhibition of BRD4 Suppresses Cell Proliferation and Induces Apoptosis in Renal Cell Carcinoma Cellular Physiology and Biochemistry Renal cell carcinoma BRD4 JQ1 Apoptosis Cell proliferation |
author_facet |
Xinchao Wu Dong Liu Xuemei Gao Fei Xie Dan Tao Xingyuan Xiao Liang Wang Guosong Jiang Fuqing Zeng |
author_sort |
Xinchao Wu |
title |
Inhibition of BRD4 Suppresses Cell Proliferation and Induces Apoptosis in Renal Cell Carcinoma |
title_short |
Inhibition of BRD4 Suppresses Cell Proliferation and Induces Apoptosis in Renal Cell Carcinoma |
title_full |
Inhibition of BRD4 Suppresses Cell Proliferation and Induces Apoptosis in Renal Cell Carcinoma |
title_fullStr |
Inhibition of BRD4 Suppresses Cell Proliferation and Induces Apoptosis in Renal Cell Carcinoma |
title_full_unstemmed |
Inhibition of BRD4 Suppresses Cell Proliferation and Induces Apoptosis in Renal Cell Carcinoma |
title_sort |
inhibition of brd4 suppresses cell proliferation and induces apoptosis in renal cell carcinoma |
publisher |
Cell Physiol Biochem Press GmbH & Co KG |
series |
Cellular Physiology and Biochemistry |
issn |
1015-8987 1421-9778 |
publishDate |
2017-04-01 |
description |
Background/Aims: Renal cell carcinoma (RCC) remains an intractable genitourinary malignancy. Resistance to chemotherapy or targeted therapies in RCC is presumably due to the complicated underlying molecular mechanisms and insufficient understanding. The aim of this research was to assess the expression and role of bromodomain-4 protein (BRD4) in RCC and evaluate the effects of BRD4 inhibitor JQ1 for RCC treatment. Methods: BRD4 expressionlevels were assessed by qRT-PCR and western blot in RCC tissues and cells. The effects of BRD4 knockdown or JQ1 on RCC cells were assessed by MTT assay and flow cytometry. The effects of in vivo treatment were evaluated through xenograft experiments. Results: BRD4 is significantly overexpressed in RCC, and is related to tumor stage and lymph node metastasis. Inhibition of BRD4 suppressed RCC cell proliferation, induced cell apoptosis in vitro and repressed tumor growth in vivo. Inhibition of BRD4 decreased BCL2 and C-MYC expression while increased BAX and cleaved caspase3 expression, and strikingly diminished the recruitment of BRD4 to BCL2 promoter. Conclusions: Our research reveals that BRD4 probably play a critical role in RCC progression, and is a new promising target for pharmacological treatment directed against this intractable disease. |
topic |
Renal cell carcinoma BRD4 JQ1 Apoptosis Cell proliferation |
url |
http://www.karger.com/Article/FullText/472407 |
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