Department of Radiation Oncology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China.
Department of Obstetrics and Gynecology, Quanzhou Medical College People's Hospital Affiliated, Quanzhou, Fujian, China.
PeerJ. 2024 Feb 23;12:e17035. doi: 10.7717/peerj.17035. eCollection 2024.
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.
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.
The inhibitory effect of JQ1 on HeLa cell proliferation increased significantly with increasing concentration and treatment time ( < 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.
JQ1 can significantly inhibit the proliferation of HeLa cells and affect the expression profile of SE-lncRNAs and mRNAs.
研究溴结构域蛋白 4(BRD4)抑制剂 JQ1 对宫颈癌(CC)HeLa 细胞中超增强子相关长链非编码 RNA(SE-lncRNA)和 mRNA 表达谱的影响。
采用 CCK8 法检测 JQ1 对 HeLa 细胞的抑制作用,探索最佳抑制浓度。分别对 JQ1 处理组和对照组细胞的 lncRNA 和 mRNA 表达谱进行全转录组测序。通过匹配获得差异表达的 SE-lncRNA,通过 Pearson 相关分析获得共表达的 mRNA。
JQ1 对 HeLa 细胞增殖的抑制作用随浓度和处理时间的增加而显著增加(<0.05)。在 0.01、0.1 和 1μmol/L 三种浓度的 JQ1 作用于 HeLa 细胞 24、48、72 和 120 h 以及 1μmol/L 的 JQ1 作用于 HeLa 细胞 72 和 120 h 的实验条件下,细胞活力相同,细胞增殖抑制作用最强。为了了解 JQ1 对 HeLa 细胞的抑制机制,本研究从 SE-lncRNA 和 mRNA 的角度分析了表达谱的差异。共鉴定出 162 个 SE-lncRNA,其中 8 个 SE-lncRNA 下调,7 个 SE-lncRNA 上调。与 SE-lncRNA 相关的差异表达 mRNAs 共 418 个,其中与 12 个 SE-lncRNA 呈正相关的 mRNAs 有 395 个,与 15 个 SE-lncRNA 呈负相关的 mRNAs 有 408 个。
JQ1 能显著抑制 HeLa 细胞的增殖,并影响 SE-lncRNA 和 mRNA 的表达谱。