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General mechanism of JQ1 in inhibiting various types of cancer

  • Authors:
    • Guojuan Jiang
    • Wanglong Deng
    • Yang Liu
    • Chengde Wang
  • View Affiliations / Copyright

    Affiliations: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P.R. China, Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
    Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1021-1034
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    Published online on: January 10, 2020
       https://doi.org/10.3892/mmr.2020.10927
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Abstract

Bromodomain‑containing 4 (BRD4) is a histone modification reader and transcriptional regulator that has been reported to interact with acetylated lysine histone motifs transcription factors (TFs), transcription co‑activators and RNA polymerase II. The selective small molecule inhibitor JQ1, which binds competitively to bromodomains, has been reported to exhibit anti‑proliferative effects in various types of cancer. Previous studies on the mechanism of action of JQ1 mostly focused on a specific tumor type or disease; however, the general mechanism through which JQ1 affects various tumors remains to be determined. In the present study, chromatin immunoprecipitation sequencing data for BRD4 and its expression profiles in six cancer cell lines were integrated and analyzed systematically. The results indicated that BRD4 binds to enhancers with histone H3 acetylated at lysine 27 (H3K27Ac) and mediator complex subunit 1 in a cell type‑specific manner, as well as binds to promoter regions with the oncogenic TFs MYC and E2F1 in a cell type‑common manner. The cell type‑common sites across the six cell types investigated were found to be functionally important for tumorigenesis, whereas the cell type‑specific sites were functionally enriched with the cell identity, all of which were sensitive to JQ1 treatment. Furthermore, a core set of JQ1‑regulated BRD4 binding genes were obtained, which were significantly inhibited by JQ1 in various cancer cell lines and contributed to hallmarks of cancer. These results implied a common mechanism underlying the therapeutic effects of JQ1 and suggested its potential suitability as an anti‑cancer drug targeting BRD4‑mediated transcriptional regulation.
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Copy and paste a formatted citation
Spandidos Publications style
Jiang G, Deng W, Liu Y and Wang C: General mechanism of JQ1 in inhibiting various types of cancer. Mol Med Rep 21: 1021-1034, 2020.
APA
Jiang, G., Deng, W., Liu, Y., & Wang, C. (2020). General mechanism of JQ1 in inhibiting various types of cancer. Molecular Medicine Reports, 21, 1021-1034. https://doi.org/10.3892/mmr.2020.10927
MLA
Jiang, G., Deng, W., Liu, Y., Wang, C."General mechanism of JQ1 in inhibiting various types of cancer". Molecular Medicine Reports 21.3 (2020): 1021-1034.
Chicago
Jiang, G., Deng, W., Liu, Y., Wang, C."General mechanism of JQ1 in inhibiting various types of cancer". Molecular Medicine Reports 21, no. 3 (2020): 1021-1034. https://doi.org/10.3892/mmr.2020.10927
Copy and paste a formatted citation
x
Spandidos Publications style
Jiang G, Deng W, Liu Y and Wang C: General mechanism of JQ1 in inhibiting various types of cancer. Mol Med Rep 21: 1021-1034, 2020.
APA
Jiang, G., Deng, W., Liu, Y., & Wang, C. (2020). General mechanism of JQ1 in inhibiting various types of cancer. Molecular Medicine Reports, 21, 1021-1034. https://doi.org/10.3892/mmr.2020.10927
MLA
Jiang, G., Deng, W., Liu, Y., Wang, C."General mechanism of JQ1 in inhibiting various types of cancer". Molecular Medicine Reports 21.3 (2020): 1021-1034.
Chicago
Jiang, G., Deng, W., Liu, Y., Wang, C."General mechanism of JQ1 in inhibiting various types of cancer". Molecular Medicine Reports 21, no. 3 (2020): 1021-1034. https://doi.org/10.3892/mmr.2020.10927
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