Institute of Preventive Medicine, School of Public Health, Dali University, Dali, Yunnan, China.
Qujing Medical College, Qujing, Yunnan, China.
Toxicol Lett. 2021 Jun 1;343:56-66. doi: 10.1016/j.toxlet.2021.02.014. Epub 2021 Feb 24.
N-methyladenosine (mA) modification and mA-modified Long non-coding RNAs (LncRNAs) play crucial roles in various pathological processes, yet their changes and relationship in cadmium-induced oxidative damage are largely unknown. Here, five mA-modified LncRNAs (LncRNA-TUG1, LncRNA-PVT1, LncRNA-MALAT1, LncRNA-XIST, LncRNA-NEAT1), which have been evidenced to involve in oxidative damage, were selected and their binding proteins were submitted to bioinformatics analysis. Our analysis results showed that these five mA-modified LncRNAs bound to different regulatory proteins of mA modification, implicating that mA modification on LncRNAs may synergistically control by multiple regulatory proteins. Furthermore, the detection data revealed that levels of mA modification, methyltransferase-like 3 (METTL3) and fat mass and obesity-associated protein (FTO) were all significantly decreased in CdSO-induced oxidative damage, which was demonstrated by increasing ROS accumulation and MDA contents as well as decreasing SOD activities. More importantly, LncRNA-MALAT1 and LncRNA-PVT1 indicated downward trend and showed positive relationship with mA modification. Collectively, our results showed that mA modification and mA-modified LncRNAs may involve in oxidative damage induced by cadmium.
N6-甲基腺苷（m6A）修饰和 m6A 修饰的长非编码 RNA（lncRNA）在各种病理过程中发挥着关键作用，但它们在镉诱导的氧化损伤中的变化和关系在很大程度上尚不清楚。在这里，选择了五个已被证明参与氧化损伤的 m6A 修饰的 lncRNA（lncRNA-TUG1、lncRNA-PVT1、lncRNA-MALAT1、lncRNA-XIST、lncRNA-NEAT1），并对其结合蛋白进行了生物信息学分析。我们的分析结果表明，这五个 m6A 修饰的 lncRNA 与 m6A 修饰的不同调节蛋白结合，表明 lncRNA 上的 m6A 修饰可能由多个调节蛋白协同控制。此外，检测数据显示，CdSO4 诱导的氧化损伤中 m6A 修饰、甲基转移酶样 3（METTL3）和肥胖相关蛋白（FTO）的水平均显著降低，这表现为 ROS 积累和 MDA 含量增加以及 SOD 活性降低。更重要的是，lncRNA-MALAT1 和 lncRNA-PVT1 呈下降趋势，并与 m6A 修饰呈正相关。综上所述，我们的结果表明，m6A 修饰和 m6A 修饰的 lncRNA 可能参与镉诱导的氧化损伤。
