Institute of Preventive Medicine, School of Public Health, Dali University, Dali, Yunnan, China.
Cell Biochem Biophys. 2024 Jun;82(2):1279-1289. doi: 10.1007/s12013-024-01282-0. Epub 2024 May 6.
N-methyladenine (mA) and 5-methylcytosine (mC) are two common forms of RNA methylation that play an important role in the epigenetics of type 2 diabetes mellitus (T2DM). One type of cell death, ferroptosis, has been implicated in islet β-cell damage in T2DM. Notably, RNA methylation, an upstream regulatory mechanism of mRNAs, can regulate the expression of ferroptosis signaling molecules, thereby affecting cell proliferation and death. Here, we found that the ferroptosis signaling pathway was activated in pancreas of T2DM rats, followed by significant changes in mA/mC modification regulatory molecules. These detection data together with the prediction results that mA and mC exist in the mRNAs of ferroptosis molecules, we speculate that mA and mC are probably involved in pancreatic cell damage by modifying of ferroptosis signaling molecules. In short, our findings provide a new research idea for future studies on the molecular mechanisms of pancreatic cell damage and point to a new direction for exploring the mechanisms of ferroptosis from the perspective of RNA methylation modification.
N6-甲基腺嘌呤(mA)和 5-甲基胞嘧啶(mC)是两种常见的 RNA 甲基化形式,它们在 2 型糖尿病(T2DM)的表观遗传学中发挥着重要作用。细胞死亡的一种形式——铁死亡,与 T2DM 中的胰岛 β 细胞损伤有关。值得注意的是,作为 mRNA 的上游调控机制之一的 RNA 甲基化可以调节铁死亡信号分子的表达,从而影响细胞的增殖和死亡。在这里,我们发现 T2DM 大鼠胰腺中的铁死亡信号通路被激活,随后 mA/mC 修饰调节分子发生显著变化。这些检测数据与 mA 和 mC 存在于铁死亡分子的 mRNAs 中的预测结果一起,我们推测 mA 和 mC 可能通过修饰铁死亡信号分子参与胰腺细胞损伤。总之,我们的研究结果为未来研究胰腺细胞损伤的分子机制提供了新的研究思路,并为从 RNA 甲基化修饰角度探索铁死亡机制指明了新的方向。