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通过诱导HOXC6 m6A修饰和通过IGF2BP2依赖机制稳定其表达,METTL3促进前列腺癌的进展
Peng He1, Xuehui Liu2, Gui Yu1
1Department of Urology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West Section 2, 1st Ring Road, Qingyang District, Chengdu, 610072, Sichuan Province, China.
Molecular and cellular biochemistry
|May 31, 2024
概括
甲基转移酶样3 (METTL3) 通过N6-甲基氨酸 (m6A) 修饰稳定Homeobox C6 (HOXC6) 表达,影响细胞生长和糖解,促进前列腺癌 (PCa).
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 前列腺癌 (PCa) 的进展与Homeobox C6 (HOXC6) 和甲基转移酶类3 (METTL3) 有关.
- 通过METTL3-介导的N6-甲基氨酸 (m6A) 修饰,HOXC6在PCa中的致癌作用的确切机制尚不清楚.
研究的目的:
- 调查HOXC6和METTL3在前列腺癌进展中的作用.
- 阐明METTL3介导的m6A修饰在调节HOXC6表达中的机制及其对PCa的影响.
主要方法:
- 细胞计数套件-8 (CCK-8),EDU,流动细胞计量,transwell,划伤和球体形成试验用于细胞分析.
- 糖解评估,RNA免疫沉降 (Me-RIP),共免疫沉降,以及体内瘤形成实验.
- 在PCa组织和细胞中分析m6A修饰,蛋白相互作用和基因表达.
主要成果:
- 在PCa组织和细胞中,HOXC6和METTL3的表达率很高.
- 沉默HOXC6或METTL3抑制了PCa细胞的增殖,入侵,迁移,干细胞和糖解.
- 通过m6A修饰,METTL3稳定了HOXC6的表达,IGF2BP2作为一个m6A读者,识别并与HOXC6mRNA结合,保持其稳定性.
结论:
- 通过m6A-IGF2BP2依赖机制稳定HOXC6表达,METTL3促进PCa的进展.
- HOXC6与糖解酶PGK1相互作用,这表明它在调节细胞代谢中的作用.
- 针对METTL3-HOXC6-IGF2BP2轴可能为前列腺癌提供治疗策略.
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