VDAC1 is Regulated by BRD4 and Contributes to JQ1 Resistance in Breast Cancer

Overview

Journal Oncol Lett

Specialty Oncology

Date 2019 Aug 28

PMID 31452730

Citations 16

Authors

Guochao Yang

Dianwei Zhou

Jun Li

Wei Wang

Wei Zhong

Wei Fan

Mancheng Yu

Hongtao Cheng

Affiliations

Soon will be listed here.

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.

Citing Articles

LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications.

Li Y, Dai Z, Cheng Z, He J, Yin Y, Liu X Heliyon. 2025; 11(3):e41934.

PMID: 39968132 PMC: 11834037. DOI: 10.1016/j.heliyon.2025.e41934.

The expression of and family genes in pituitary adenomas: clinical correlations and postsurgical outcomes.

Facundo A, Magalhaes M, Nascimento G, Azulay R, Santos R, Freitas L Front Endocrinol (Lausanne). 2024; 15:1481050.

PMID: 39449743 PMC: 11499145. DOI: 10.3389/fendo.2024.1481050.

BET inhibitors (BETi) influence oxidative phosphorylation metabolism by affecting mitochondrial dynamics leading to alterations in apoptotic pathways in triple-negative breast cancer (TNBC) cells.

Rossi T, Iorio E, Chirico M, Pisanu M, Amodio N, Gallo Cantafio M Cell Prolif. 2024; 57(12):e13730.

PMID: 39223828 PMC: 11628750. DOI: 10.1111/cpr.13730.

Construction of a prognostic score model for breast cancer based on multi-omics analysis of study on bone metastasis.

Ren H, Shen X, Xie M, Guo X Transl Cancer Res. 2024; 13(5):2419-2436.

PMID: 38881940 PMC: 11170530. DOI: 10.21037/tcr-23-1881.

Role and regulation of FOXO3a: new insights into breast cancer therapy.

Mei W, Mei B, Chang J, Liu Y, Zhou Y, Zhu N Front Pharmacol. 2024; 15:1346745.

PMID: 38505423 PMC: 10949727. DOI: 10.3389/fphar.2024.1346745.

References

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

Castagna A, Antonioli P, Astner H, Hamdan M, Righetti S, Perego P . A proteomic approach to cisplatin resistance in the cervix squamous cell carcinoma cell line A431. Proteomics. 2004; 4(10):3246-67. DOI: 10.1002/pmic.200400835. View

Shoshan-Barmatz V, Israelson A, Brdiczka D, Sheu S . The voltage-dependent anion channel (VDAC): function in intracellular signalling, cell life and cell death. Curr Pharm Des. 2006; 12(18):2249-70. DOI: 10.2174/138161206777585111. View

Jung J, Han C, Jeong Y, Kim H, Lim H, Lee K . Epigallocatechin gallate inhibits nitric oxide-induced apoptosis in rat PC12 cells. Neurosci Lett. 2006; 411(3):222-7. DOI: 10.1016/j.neulet.2006.09.089. View

Nawarak J, Huang-Liu R, Kao S, Liao H, Sinchaikul S, Chen S . Proteomics analysis of A375 human malignant melanoma cells in response to arbutin treatment. Biochim Biophys Acta. 2008; 1794(2):159-67. DOI: 10.1016/j.bbapap.2008.09.023. View

Thinnes F . Neuroendocrine differentiation of LNCaP cells suggests: VDAC in the cell membrane is involved in the extrinsic apoptotic pathway. Mol Genet Metab. 2009; 97(4):241-3. DOI: 10.1016/j.ymgme.2009.04.010. View

Seyfried T, Shelton L . Cancer as a metabolic disease. Nutr Metab (Lond). 2010; 7:7. PMC: 2845135. DOI: 10.1186/1743-7075-7-7. View

Shoshan-Barmatz V, De Pinto V, Zweckstetter M, Raviv Z, Keinan N, Arbel N . VDAC, a multi-functional mitochondrial protein regulating cell life and death. Mol Aspects Med. 2010; 31(3):227-85. DOI: 10.1016/j.mam.2010.03.002. View

Delmore J, Issa G, Lemieux M, Rahl P, Shi J, Jacobs H . BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011; 146(6):904-17. PMC: 3187920. DOI: 10.1016/j.cell.2011.08.017. View

10.

Shoshan-Barmatz V, Mizrachi D . VDAC1: from structure to cancer therapy. Front Oncol. 2012; 2:164. PMC: 3516065. DOI: 10.3389/fonc.2012.00164. View

11.

Pathmanathan N, Balleine R . Ki67 and proliferation in breast cancer. J Clin Pathol. 2013; 66(6):512-6. DOI: 10.1136/jclinpath-2012-201085. View

12.

Weisthal S, Keinan N, Ben-Hail D, Arif T, Shoshan-Barmatz V . Ca(2+)-mediated regulation of VDAC1 expression levels is associated with cell death induction. Biochim Biophys Acta. 2014; 1843(10):2270-81. DOI: 10.1016/j.bbamcr.2014.03.021. View

13.

Arif T, Vasilkovsky L, Refaely Y, Konson A, Shoshan-Barmatz V . Silencing VDAC1 Expression by siRNA Inhibits Cancer Cell Proliferation and Tumor Growth In Vivo. Mol Ther Nucleic Acids. 2014; 3:e159. PMC: 4011124. DOI: 10.1038/mtna.2014.9. View

14.

Dong L, Neuzil J . Mitochondria in cancer: why mitochondria are a good target for cancer therapy. Prog Mol Biol Transl Sci. 2014; 127:211-27. DOI: 10.1016/B978-0-12-394625-6.00008-8. View

15.

Bhat T, Kumar S, Chaudhary A, Yadav N, Chandra D . Restoration of mitochondria function as a target for cancer therapy. Drug Discov Today. 2015; 20(5):635-43. PMC: 4433775. DOI: 10.1016/j.drudis.2015.03.001. View

16.

Leone A, Roca M, Ciardiello C, Terranova-Barberio M, Vitagliano C, Ciliberto G . Vorinostat synergizes with EGFR inhibitors in NSCLC cells by increasing ROS via up-regulation of the major mitochondrial porin VDAC1 and modulation of the c-Myc-NRF2-KEAP1 pathway. Free Radic Biol Med. 2015; 89:287-99. DOI: 10.1016/j.freeradbiomed.2015.07.155. View

17.

Zhang G, Jiang G, Wang C, Zhong K, Zhang J, Xue Q . Decreased expression of microRNA-320a promotes proliferation and invasion of non-small cell lung cancer cells by increasing VDAC1 expression. Oncotarget. 2016; 7(31):49470-49480. PMC: 5226522. DOI: 10.18632/oncotarget.9943. View

18.

Zhang C, Ding W, Liu Y, Hu Z, Zhu D, Wang X . Proteomics-based identification of VDAC1 as a tumor promoter in cervical carcinoma. Oncotarget. 2016; 7(32):52317-52328. PMC: 5239554. DOI: 10.18632/oncotarget.10562. View

19.

Freitas S, Martins R, Costa M, Leao P, Vitorino R, Vasconcelos V . Hierridin B Isolated from a Marine Cyanobacterium Alters VDAC1, Mitochondrial Activity, and Cell Cycle Genes on HT-29 Colon Adenocarcinoma Cells. Mar Drugs. 2016; 14(9). PMC: 5039529. DOI: 10.3390/md14090158. View

20.

Fitzmaurice C, Allen C, Barber R, Barregard L, Bhutta Z, Brenner H . Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol. 2016; 3(4):524-548. PMC: 6103527. DOI: 10.1001/jamaoncol.2016.5688. View