全癌症转录组分析揭示了通过替代串联转录启动的广泛调节
Zhaozhao Zhao1,2, Yu Chen1, Xudong Zou3
1State Key Laboratory of Genetic Engineering, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Collaborative Innovation Center of Genetics and Development, Human Phenome Institute, Center for Evolutionary Biology, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Sciences, Fudan University, Shanghai 200438, China.
Science advances
|July 10, 2024
概括
癌症中的替代转录启动部位 (TSS) 失调,影响基因表达. 这项研究揭示了tandem TSS的使用是癌症相关的转录组变化的新层,影响细胞增殖和迁移.
科学领域:
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
- 文字转录学 (Transcriptomics) 是一个学科.
背景情况:
- 异常的转录启动,特别是来自替代的第一个外原体,与瘤发生有关.
- 替代串联转录启动在癌症基因调节中的作用和患病率在很大程度上仍未被探索.
研究的目的:
- 开发一种用于分析替代串联转录起点 (TSS) 使用的计算方法.
- 调查失调的双重TSS在癌症中的使用率和影响.
主要方法:
- 开发了一种计算方法来分析从RNA测序数据的替代串联TSS使用.
- 将该方法应用于泛癌RNA测序数据集.
- 研究了双重TSS动态和表观基因组调制之间的关联.
主要成果:
- 在各种癌症类型中观察到TSS协同使用的广泛失调.
- 识别了独立于整体表达水平或替代性第一个外子体使用的协同TSS失调.
- 证明TIMP13的5'非翻译区域缩短增加了蛋白质的产生,促进了肺癌细胞的增殖和迁移.
结论:
- 失调的协同TSS使用代表了癌症相关的转录组变化的显著,以前被低估的层.
- 协同TSS动态与表观基因组变化有关,并且可以影响关键的癌细胞行为.
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