在P300/SP1复合体中介的高METTL1通过CRPC的内部m7G修饰来调节CDK14mRNA稳定性
Mingpeng Zhang1, Duo Kan1, Boya Zhang2
1Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin, 300211, China.
Journal of experimental & clinical cancer research : CR
|August 20, 2023
概括
由METTL1介导的N7-甲基瓜诺辛 (m7G) 修饰促进前列腺癌的进展. 在割抗性前列腺癌 (CRPC) 中,METTL1被上调,通过稳定CDK14mRNA来驱动瘤生长和入侵.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子瘤学分子瘤学
- 在RNA生物学,RNA生物学.
背景情况:
- N7-甲基瓜诺辛 (m7G) 是一种普遍存在的RNA修饰,影响着各种RNA类型和过程.
- 虽然m7G在转录,tRNA稳定性,rRNA处理和miRNA生物合成中的作用已知,但其在mRNA和癌症中的甲基转移酶METTL1中的功能,特别是前列腺癌 (PCa),仍然不清楚.
研究的目的:
- 研究METTL1和m7G修饰在前列腺癌 (PCa) 进展中的作用.
- 阐明METTL1的监管机制及其PCa下游目标.
主要方法:
- RNA测序 (RNA-seq) 和体外实验用于比较激素敏感 (HSPC) 和割抗性前列腺癌 (CRPC) 中的METTL1水平.
- 在体外和体内测试以评估METTL1对CRPC进展的功能影响.
- 染色体免疫沉定量逆转录聚合酶连锁反应 (CHIP-qPCR),共免疫沉 (Co-IP),光酶记者测定,转录组测序,m7G AlkAniline-Seq和mRNA降解实验以探索分子机制.
主要成果:
- 在CRPC中METTL1表达升高,与患者预后不佳相关.
- 抑制METTL1显著抑制CRPC细胞的增殖和侵入.
- 在CRPC中,P300/SP1复合体对METTL1的转录进行上调.
- METTL1通过m7G修饰增强CDK14mRNA的稳定性,促进CRPC的进展.
结论:
- METTL1是CRPC进展的一个关键驱动因素.
- 向METTL1可能为前列腺癌提供治疗策略.
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