长非编码RNA中的瘤突变增强了细胞的适应性
Roberta Esposito1,2,3, Andrés Lanzós4,5,6, Tina Uroda7,8
1Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, 3010, Bern, Switzerland. roberta.esposito@unibe.ch.
Nature communications
|June 8, 2023
概括
长非编码RNA (lncRNAs) 的体质突变可以通过改变瘤细胞适应性来驱动癌症. 这项研究确定了54个驱动性lncRNAs,包括NEAT1,证明了它们在癌症进展中的作用.
科学领域:
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
- 分子瘤学分子瘤学
背景情况:
- 长非编码RNAs (lncRNAs) 与癌症有关,主要是通过改变表达水平.
- 影响瘤细胞适应性的lncRNAs功能改变的体质突变的作用在很大程度上仍未被探索.
研究的目的:
- 为了识别长非编码RNAs (lncRNAs) 携带促进癌症的体位突变.
- 研究这些突变对瘤细胞健康和癌症进展的功能影响.
主要方法:
- 在2583个初级和3527个转移性瘤中对单核酸变体 (SNV) 的全基因组分析,以确定 lncRNAs 中的适应性改变SNV.
- 实验室中对候选 lncRNAs 的过度表达研究,以评估它们对瘤细胞增殖的影响.
- 在细胞突变和小鼠模型中评估NEAT1SNVs的功能意义.
- 机制研究以阐明NEAT1 SNVs如何影响其核糖蛋白结构和斑形成.
主要成果:
- 确定了54个被积极选择和突变的lncRNAs,以已知的癌症基因和临床特征进行丰富.
- 证明过度表达几个已识别的 lncRNAs 在体外促进瘤细胞的增殖.
- 在NEAT1瘤基因中证实了SNVs的热点,具有类似瘤的突变,在体外和体内显著增加了细胞适应性.
- 揭示了NEAT1 SNVs重塑其核蛋白复合体,导致增强光斑的形成.
结论:
- 驱动器突变分析是发现促进癌症的lncRNAs的一个有价值的方法.
- 像NEAT1这样的lncRNA体内突变可以通过改变它们的结构和功能来直接提高病态癌细胞的适应性.
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