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Genome-wide transcriptional analysis of BRD4-regulated genes and pathways in human glioma U251 cells

  • Authors:
    • Zhanhui Du
    • Xiuxiang Song
    • Fangfang Yan
    • Jingjing Wang
    • Yuxia Zhao
    • Shangming Liu
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    Affiliations: The Key Laboratory of Cardiovascular Remodelling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Anaesthesiology, The People's Hospital of Jimo City, Qingdao, Shandong 266200, P.R. China, Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China, Institute of Pathology and Pathophysiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China
    Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1415-1426
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    Published online on: March 16, 2018
       https://doi.org/10.3892/ijo.2018.4324
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Abstract

Bromodomain containing 4 (BRD4), a member of the bromodomain and extra-terminal family, has become a promising drug target for numerous types of cancer. BRD4 has been reported to be deregulated in gliomas; however, the precise molecular pathways regulated by BRD4 remained elusive. In the present study, BRD4 expression was silenced in the glioma cell line U251 and the results demonstrated that BRD4 knockdown attenuated cell proliferation and promoted cell apoptosis. A genome-wide analysis of BRD4-regulated transcripts in U251 cells was performed using microarray to reveal the possible molecular mechanism. A total of 3,529 differentially expressed genes were identified; 1,648 of these genes were upregulated and 1,881 were downregulated. The results of the gene ontology analysis revealed that these genes were mainly involved in membrane organization, mitotic cell cycle, cell division and DNA replication. Pathway analysis revealed that the pathways altered following BRD4 knockdown included multiple cellular processes, such as cell cycle and apoptosis. Candidate genes were identified through global signal transduction network analysis and were validated using reverse transcription-quantitative polymerase chain reaction and western blot analyses. The results demonstrated that BRD4 knockdown decreased the expression of KRAS proto-oncogene GTPase (KRAS). Downregulated KRAS expression in U251 cells restrained cell proliferation and promoted cell apoptosis, suggesting that the effect of BRD4 on glioma cells might occur through the Ras pathway. In conclusion, the present results confirmed the role of BRD4 in glioma and provided information for further exploration of the molecular mechanism of BRD4 in glioma development and progression.
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Copy and paste a formatted citation
Spandidos Publications style
Du Z, Song X, Yan F, Wang J, Zhao Y and Liu S: Genome-wide transcriptional analysis of BRD4-regulated genes and pathways in human glioma U251 cells. Int J Oncol 52: 1415-1426, 2018.
APA
Du, Z., Song, X., Yan, F., Wang, J., Zhao, Y., & Liu, S. (2018). Genome-wide transcriptional analysis of BRD4-regulated genes and pathways in human glioma U251 cells. International Journal of Oncology, 52, 1415-1426. https://doi.org/10.3892/ijo.2018.4324
MLA
Du, Z., Song, X., Yan, F., Wang, J., Zhao, Y., Liu, S."Genome-wide transcriptional analysis of BRD4-regulated genes and pathways in human glioma U251 cells". International Journal of Oncology 52.5 (2018): 1415-1426.
Chicago
Du, Z., Song, X., Yan, F., Wang, J., Zhao, Y., Liu, S."Genome-wide transcriptional analysis of BRD4-regulated genes and pathways in human glioma U251 cells". International Journal of Oncology 52, no. 5 (2018): 1415-1426. https://doi.org/10.3892/ijo.2018.4324
Copy and paste a formatted citation
x
Spandidos Publications style
Du Z, Song X, Yan F, Wang J, Zhao Y and Liu S: Genome-wide transcriptional analysis of BRD4-regulated genes and pathways in human glioma U251 cells. Int J Oncol 52: 1415-1426, 2018.
APA
Du, Z., Song, X., Yan, F., Wang, J., Zhao, Y., & Liu, S. (2018). Genome-wide transcriptional analysis of BRD4-regulated genes and pathways in human glioma U251 cells. International Journal of Oncology, 52, 1415-1426. https://doi.org/10.3892/ijo.2018.4324
MLA
Du, Z., Song, X., Yan, F., Wang, J., Zhao, Y., Liu, S."Genome-wide transcriptional analysis of BRD4-regulated genes and pathways in human glioma U251 cells". International Journal of Oncology 52.5 (2018): 1415-1426.
Chicago
Du, Z., Song, X., Yan, F., Wang, J., Zhao, Y., Liu, S."Genome-wide transcriptional analysis of BRD4-regulated genes and pathways in human glioma U251 cells". International Journal of Oncology 52, no. 5 (2018): 1415-1426. https://doi.org/10.3892/ijo.2018.4324
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