Effects of BRD4 inhibitor JQ1 on the expression profile of super-enhancer related lncRNAs and mRNAs in cervical cancer HeLa cells

PeerJ. 2024 Feb 23:12:e17035. doi: 10.7717/peerj.17035. eCollection 2024.

Abstract

Objective: To investigate the effects of bromine domain protein 4 (BRD4) inhibitor JQ1 on the expression profile of super-enhancer-related lncRNAs (SE-lncRNAs) and mRNAs in cervical cancer (CC) HeLa-cells.

Methods: The CCK8 method was implemented to detect the inhibitory effect of JQ1 on HeLa cells and explore the best inhibitory concentration. Whole transcriptome sequencing was performed to detect the changes of lncRNAs and mRNAs expression profiles in cells of the JQ1 treatment group and control group, respectively. The differentially expressed SE-lncRNAs were obtained by matching, while the co-expressed mRNAs were obtained by Pearson correlation analysis.

Results: The inhibitory effect of JQ1 on HeLa cell proliferation increased significantly with increasing concentration and treatment time (P < 0.05). Under the experimental conditions of three concentrations of 0.01, 0.1 and 1 μmol/L of JQ1 on HeLa cells at 24, 48, 72 and 120 h, 1 μmol/L of JQ1 at 72 and 120 h had the same cell viability and the strongest cell proliferation inhibition. In order to understand the inhibitory mechanism of JQ1 on HeLa cells, this study analyzed the expression profile differences from the perspective of SE-lncRNAs and mRNAs. A total of 162 SE-lncRNAs were identified, of which 8 SE-lncRNAs were down-regulated and seven SE-lncRNAs were up-regulated. A total of 418 differentially expressed mRNAs related to SE-lncRNAs were identified, of which 395 mRNAs had positive correlation with 12 SE-lncRNAs and 408 mRNAs had negative correlation with 15 SE-lncRNAs.

Conclusion: JQ1 can significantly inhibit the proliferation of HeLa cells and affect the expression profile of SE-lncRNAs and mRNAs.

Keywords: BRD4 inhibitor; Cervical cancer; HeLa cells; JQ1; RNA-Seq; Super-enhancer related lncRNAs.

MeSH terms

  • Bromodomain Containing Proteins
  • Cell Cycle Proteins / genetics
  • Female
  • HeLa Cells
  • Humans
  • Nuclear Proteins / genetics
  • RNA, Long Noncoding* / genetics
  • RNA, Messenger / genetics
  • Transcription Factors / genetics
  • Uterine Cervical Neoplasms* / drug therapy

Substances

  • Nuclear Proteins
  • Transcription Factors
  • RNA, Long Noncoding
  • RNA, Messenger
  • BRD4 protein, human
  • Bromodomain Containing Proteins
  • Cell Cycle Proteins

Grants and funding

This study was supported by Joint Funds for the innovation of science and Technology, Fujian province (Grant No: 2023Y, Jianqing Zheng), the Fujian provincial health technology project (Youth Scientific Research Project, 2019-1-50 to Jianqing Zheng), the Nursery Fund Project of the Second Affiliated Hospital of Fujian Medical University (Grant No: 2021MP05 to Jianqing Zheng) and the Science and Technology projects of Quanzhou city (Grant No: 2023NS010 to Jianqing Zheng). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.