Noncoding RNA Laboratory, Department of Molecular Biology and Genetics, İzmir Institute of Technology, 35430 Urla İzmir, Turkey.
Cells. 2022 Dec 2;11(23):3905. doi: 10.3390/cells11233905.
Cisplatin (CP), which is a conventional cancer chemotherapeutic drug, induces apoptosis by modulating a diverse array of gene regulatory mechanisms. However, cisplatin-mediated changes in the mA methylome are unknown. We employed an mA miCLIP-seq approach to investigate the effect of mA methylation marks under cisplatin-mediated apoptotic conditions on HeLa cells. Our high-resolution approach revealed numerous mA marks on 972 target mRNAs with an enrichment on 132 apoptotic mRNAs. We tracked the fate of differentially methylated candidate mRNAs under knockdown and cisplatin treatment conditions. Polysome profile analyses revealed perturbations in the translational efficiency of and transcripts. Congruently, amounts were dependent on . Additionally, cisplatin-mediated apoptosis was sensitized by knockdown. These results suggest that apoptotic pathways are modulated by mA methylation events and that the axis modulates cisplatin-mediated apoptosis in HeLa cells.
顺铂（CP）是一种传统的癌症化疗药物，通过调节多种基因调控机制诱导细胞凋亡。然而，顺铂介导的 mA 甲基化组的变化尚不清楚。我们采用 mA miCLIP-seq 方法研究了 mA 甲基化标记在顺铂介导的细胞凋亡条件下对 HeLa 细胞的影响。我们的高分辨率方法在 132 个凋亡相关 mRNAs 上发现了大量 mA 标记，并在 972 个靶 mRNAs 上进行了富集。我们在 和 cisplatin 处理条件下对差异甲基化候选 mRNAs 的命运进行了跟踪。多核糖体谱分析显示 和 转录物的翻译效率受到干扰。一致地， 的含量取决于 。此外， 的敲低可使顺铂介导的细胞凋亡更加敏感。这些结果表明，细胞凋亡途径受 mA 甲基化事件的调节，并且 轴在 HeLa 细胞中调节顺铂介导的细胞凋亡。
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