酸化的SHMT2通过m6对肺腺癌的修改来调节瘤发生
Tianyu Han1,2,3, Yanan Wang1,2,3, Minzhang Cheng1,2,3
1Jiangxi Institute of Respiratory Disease, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, Jiangxi, 330006, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|March 9, 2024
概括
向氨酸氧甲基转移酶2 (SHMT2) 是肺腺癌 (LUAD) 的新策略. 由MAPK1驱动的SHMT2的升级促进了LUAD. 抑制SHMT2通过降低RNA甲基化来减少瘤生长.
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:
- 准癌症代谢是关键的治疗策略.
- 肺腺癌 (LUAD) 具有特定的代谢脆弱性.
- 血清基甲基转移酶1/2 (SHMT1/2) 是LUAD中潜在的代谢标.
研究的目的:
- 使用化合物库在LUAD中选代谢点.
- 阐明在LUAD中SHMT2的调节机制.
- 调查在LUAD中准SHMT2的治疗潜力.
主要方法:
- 化合物库对代谢酶抑制剂的选.
- 通过MAPK1-介导的酸化来研究SHMT2上调机制.
- 评估SHMT2-Ser90脱化对S-adenosylmethionine和m6A水平的影响.
- 使用MeRIP-Seq和RNA-Seq分析RNA的修饰和降解.
主要成果:
- 作为SHMT1/2抑制剂的SHIN1,特别抑制了依赖于SHMT2过度表达的LUAD细胞.
- 在Ser90中通过MAPK1-介导的酸化通过抑制STUB1-介导的降解来稳定SHMT2.
- 通过SHMT2-Ser90脱化,降低了S-adenosylmethionine和全球m6ARNA水平.
- 抑制SHMT2加速瘤基因RNA降解,抑制瘤发生.
结论:
- 在LUAD瘤发生过程中发现了SHMT2的新型调节机制.
- 通过MAPK1介导的SHMT2酸化对LUAD进展至关重要.
- 向SHMT2代表了LUAD的一个有前途的治疗策略.
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