VDAC1 is regulated by BRD4 and contributes to JQ1 resistance in breast cancer

Yang,Guochao; Zhou,Dianwei; Li,Jun; Wang,Wei; Zhong,Wei; Fan,Wei; Yu,Mancheng; Cheng,Hongtao

doi:10.3892/ol.2019.10534

VDAC1 is regulated by BRD4 and contributes to JQ1 resistance in breast cancer

Authors:
- Guochao Yang
- Dianwei Zhou
- Jun Li
- Wei Wang
- Wei Zhong
- Wei Fan
- Mancheng Yu
- Hongtao Cheng
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Affiliations: Department of General Surgery, Rongjun Hospital, Wuhan, Hubei 430079, P.R. China, Department of Gastrointestinal Surgery, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, Hubei 437100, P.R. China, Department of Surgery, Clinical Medical College, Hubei University of Science and Technology, Xianning, Hubei 437100, P.R. China, Department of Breast Surgery, Hubei Cancer Hospital, Wuhan, Hubei 430079, P.R. China
Published online on: June 27, 2019 https://doi.org/10.3892/ol.2019.10534
Pages: 2340-2347
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Voltage‑dependent anion channels (VDACs) are situated in the outer membrane of the mitochondria and serve as gatekeepers that control metabolite and ion exchange between the cytosol and mitochondria. VDAC1 is one of the most studied members of the VDAC protein family and is overexpressed in multiple types of cancer. However, the specific biological function and regulatory mechanism of VDAC1 in breast cancer remains unclear. The present study investigated the biological role of VDAC1 in breast cancer cells using an MTS assay. The association of clinicopathological features with VDAC1 in breast cancer was analyzed by Gene Expression Profiling Interactive Analysis. The regulatory mechanism of VDAC1 was determined by cell transfection, western blot analysis, reverse transcription‑quantitative (q)PCR analysis, chromatin immunoprecipitation (ChIP) and ChIP‑qPCR analysis. The results of the present study demonstrated that VDAC1 promoted breast cancer proliferation and was associated with a poor prognosis in patients with breast cancer. Additionally, it was observed that the expression of VDAC1 could be decreased by the bromodomain inhibitor (JQ1), and bromodomain‑containing protein 4 (BRD4) was indicated to be a regulator of VDAC1. Furthermore, results suggested that VDAC1 may be involved in the resistance of breast cancer to JQ1. Collectively, the present findings uncovered important aspects of the function of VDAC1 in the tumor progression of breast cancer, and may provide a basis for potential therapeutic strategies for the treatment of breast cancer.

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