在长期缺氧的情况下,METTL3通过PLOD2 m6的A-甲基化促进细胞癌的进展
Yimeng Chen1, Yichen He1, Zhengsheng Li1
1Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China.
Cell death & disease
|January 17, 2024
概括
低氧促进细胞癌 (RCC) 通过METTL3-驱动的PLOD2表达的进展. 用像STM2457这样的抑制剂向METTL3,在RCC中显示出抗瘤效应.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- N6-甲基氨酸 (m6A) 是一种关键的mRNA修饰,影响基因表达和癌症.
- METTL3,一种m6甲基转移酶,与各种癌症有关,包括细胞癌 (RCC).
研究的目的:
- 研究METTL3在细胞癌 (RCC) 中的作用和调控机制.
- 探索METTL3在RCC细胞增殖,迁移和入侵中的功能.
主要方法:
- 评估了RCC组织中的METTL3表达,并将其与预后相关联.
- 研究了METTL3在RCC细胞增殖,迁移和入侵中的甲基酶活性.
- 研究了METTL3转录的低氧诱导因子1-α (HIF-1α) 调节.
- 分析的METTL3介导的m6是PLOD2mRNA的修改.
- 使用METTL3抑制剂STM2457和AV9-介导的PLOD2再转导在体外和体内RCC模型.
主要成果:
- 晚期RCC中METTL3表达升级,并与预后不佳有关.
- 通过其甲基酶活性,METTL3增强了RCC细胞的增殖,迁移和入侵.
- 缺氧诱导HIF-1α与METTL3促进体结合,增加其转录.
- METTL3以一种m-依赖的方式促进了PLOD2的表达和翻译.
- 抑制METTL3 (STM2457) 降低了瘤生长;PLOD2重新表达抵消了这种效应.
结论:
- 低氧驱动的METTL3转录通过通过m6A修改升调PLOD2表达来促进RCC进展.
- METTL3代表了细胞癌的潜在治疗标.
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