N4-乙基丁修改了用于癌细胞中处理的初级microRNA
Hailong Zhang1,2, Runhui Lu1, Jiayi Huang1
1Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Cellular and molecular life sciences : CMLS
|February 3, 2024
概括
研究人员发现,N4乙基丁 (ac4C) 修饰发生在初级microRNAs (pri-miRNAs) 上,影响其处理. 这一发现揭示了NAT10的存在.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症研究 癌症研究
背景情况:
- N4乙基 (ac4C) 修饰对于遗传信息表达至关重要,主要是在tRNA,rRNA和mRNA上.
- 在microRNAs (miRNAs) 中ac4C修饰的作用及其生理/病理功能在很大程度上是未知的.
研究的目的:
- 为了研究微RNA是否经历了ac4C修饰.
- 阐明NAT10/THUMPD1在primi-miRNA ac4C修饰中的作用.
- 探索pri-miRNA ac4C对miRNA生物发生和癌症进展的影响.
主要方法:
- 鉴定NAT10/THUMPD1作为负责pri-miRNAs中ac4C修饰的酶.
- 对NAT10进行实验性操纵 (敲击),以评估其对primiRNA和成熟miRNA表达水平的影响.
- 分子机制研究分析了pri-miRNA,DGCR8和前-miRNA的处理之间的相互作用.
- 在临床癌症样本中分析NAT10表达及其与患者预后的相关性.
主要成果:
- 鉴定出NAT10/THUMPD1是一种酶,它用ac4C.ac4C.ac4C与初级微RNA (pri-miRNAs) 进行乙化.
- NAT10的淘汰导致成熟miRNA的减少和primiRNA水平的增加.
- 在pri-miRNA上的ac4C修改通过改善pri-miRNA-DGCR8相互作用,促进成熟miRNA生物发生,增强其转化为前体miRNA (pre-miRNA) 的过程.
- 通过miRNA生产调节,NAT10敲击降低了肺癌细胞的瘤特征.
- 在各种癌症中,NAT10的表达很高,并且与预后不佳有关.
结论:
- 通过调节pri-miRNAs的ac4C修饰,NAT10在癌症发病和进展中发挥着关键作用,从而影响miRNA的产生.
- 向NAT10通过影响miRNA生物发生提供了潜在的癌症治疗策略.
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