通过激活JAK1/STAT3信号通路,METTL3促进结直肠癌的进展
Yuechao Sun1, Weipeng Gong2, Song Zhang3
1Ningbo Institute of Life and Health Industry, Chinese Academy of Sciences, Ningbo, Zhejiang, The People's Republic of China.
Cell death & disease
|November 24, 2023
概括
甲基转移酶样3 (METTL3) 驱动着结直肠癌,通过N6-甲基氨酸 (m6A) 修饰和直接转录控制来调节基因表达,影响关键癌症途径.
科学领域:
- 分子瘤学分子瘤学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症生物学 癌症生物学
背景情况:
- 在各种癌症中,N6-甲基氨酸 (m6A) 修饰的作用,特别是METTL3的作用,是公认的.
- 在结直肠癌进展中METTL3的特定机制在很大程度上仍未被定义.
研究的目的:
- 阐明甲基转移酶类3 (METTL3) 在结直肠癌中的双重作用.
- 研究METTL3在基因调节和癌症恶性病变中的依赖甲基转移酶和独立功能.
主要方法:
- 分析METTL3表达及其在结直肠癌中的m6A修饰活性.
- 研究了METTL3与JAK1,STAT3以及下游效应因子 (如VEGFA和CCND1.1) 的相互作用.
- 评估了METTL3对p-STAT3信号通路,细胞增殖和转移 in vitro 和 in vivo 的影响.
主要成果:
- 在结直肠癌中,上调的METTL3表现出A-依赖和A-独立的功能.
- METTL3通过m6A修改促进JAK1转化,并独立于其甲基转移酶活性增强STAT3转录.
- 在METTL3驱动的JAK1-STAT3通路的激活上调 VEGFA 和 CCND1,促进癌细胞的增殖和转移.
结论:
- 在结直肠癌中,METTL3充当双重调节剂,同时作为m6A编写剂和转录调节剂.
- METTL3的联合作用通过JAK1-STAT3信号通路驱动结直肠癌恶性病变.
- 向METTL3可能为结直肠癌提供一种新的治疗策略.
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