通过WTAP介导的m6A修改TRAIL-DR4抑制MH7A细胞亡
Xiaoya Cui1,2, Fengxia Xu1,3, Xue Pang1,3
1The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China.
International journal of rheumatic diseases
|January 11, 2025
概括
威尔姆斯瘤1-关联蛋白 (WTAP) 在表观遗传上修改了与TNF相关的诱导亡的联结体死亡受体4 (TRAIL-DR4) mRNA,抑制了类风湿性关节炎 (RA) 细胞中的亡. 这一发现揭示了RA治疗的新型治疗标.
科学领域:
- 表观遗传学和RNA修饰
- 自身免疫性疾病的分子机制
背景情况:
- N6-甲基氨酸 (m6A) 是一种关键的RNA修饰,参与了诸如亡和增殖等生物过程.
- 威尔姆斯瘤1-关联蛋白 (WTAP) 是一个关键的m6A调节器,与细胞增殖和细胞亡有关.
- 在风湿性关节炎 (RA) 中WTAP的作用,其特征是突性增生,仍然在很大程度上未被探索.
研究的目的:
- 调查WTAP介导的m6A修饰TNF相关的诱导亡的联结体死亡受体4 (TRAIL-DR4) 在RA中的作用.
- 阐明WTAP对RA突发性关节细胞中细胞过程的影响.
主要方法:
- 在MH7A细胞中使用等离子体和小干扰RNA过度表达和沉默WTAP.
- 评估基因和蛋白质表达 (WTAP,BCL2,BAX,TRAIL-DR4) 通过免疫光学,RT-qPCR和西方斑点.
- 使用CCK-8,流细胞计和TEM评估细胞活力,细胞循环,细胞亡和增殖.
- 使用MeRIP-qPCR和actinomycin D测试验证TRAIL-DR4 m6A修饰和mRNA稳定性的验证.
主要成果:
- 过度表达WTAP增加了WTAP和BCL2水平,降低了BAX和TRAIL-DR4水平,抑制了细胞亡,并促进了MH7A细胞的细胞活力和增殖.
- 沉默WTAP产生了相反的效果,突出了WTAP的支持生存的作用.
- 发现WTAP促进了TRAIL-DR4 m6A的修饰,降低了TRAIL-DR4 mRNA的稳定性,并随后抑制了亡.
结论:
- 通过WTAP介导的TRAIL-DR4的m6A修饰抑制了RA的突细胞 (MH7A) 中的亡.
- 这种机制为RA提供了一个新的治疗点.
- 这些发现通过m6A变化的镜头来扩大对RA病理生理学的理解.
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