通过双M介导的TROP2翻译
Cong Chen1, Yinghui Chao2, Chengcheng Zhang1
1Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Cancer letters
|June 2, 2023
概括
双重RNA修饰,信使RNAN6-腺氨酸甲基化 (m6A) 和转移RNA7-甲基氨酸 (m7G),通过增强瘤基因TROP2转化促进膀癌症 (BCa). 向METTL3和METTL1可以抑制BCa的进展.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症研究 癌症研究
背景情况:
- 像m6A和m7G这样的RNA修饰对于RNA功能至关重要.
- 双重m6A/m7G修饰在膀癌 (BCa) 基因翻译中的协同作用尚不清楚.
研究的目的:
- 阐明双重m6A/m7GRNA修饰促进TROP2转化和BCa发育的机制.
- 研究向这些RNA表观遗传通路的治疗潜力.
主要方法:
- 研究了TROP2mRNA的METTL3-介导的m6A修饰和tRNA的METTL1-介导的m7G修饰.
- 评估了TROP2抑制和METTL3/METTL1淘汰对BCa细胞 in vitro和 in vivo行为的影响.
- 在BCa患者中分析了TROP2,METTL3和METTL1表达之间的相关性.
主要成果:
- METTL3通过m6A修饰促进TROP2mRNA转换,而METTL1通过tRNAm7G修饰增强它.
- 抑制TROP2或联合淘汰METTL3/METTL1抑制了BCa细胞的增殖,入侵和迁移.
- 在患者中,TROP2过度表达部分挽救了METTL3/METTL1淘汰的抑制作用,TROP2水平与METTL3和METTL1正相关.
结论:
- 通过METTL3和METTL1介导的双重m6A/m7GRNA修改协同增强TROP2转化,推动BCa的进展.
- 这项研究揭示了膀癌中一种新的RNA表观遗传机制,突出了TROP2,METTL3和METTL1作为潜在的治疗点.
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