在单细胞分辨率下对人类结直肠癌中全长RNA异型的系统性表征
Ping Lu1,2,3, Yu Zhang1,2,3, Yueli Cui1,2
1Biomedical Pioneering Innovative Center, School of Life Sciences, Department of General Surgery, Third Hospital, Peking University, Beijing 100871, China.
Protein & cell
|July 24, 2025
概括
这项研究使用单细胞测序揭示了结直肠癌 (CRC) 中复杂的RNA拼接变化. 这些基因表达的改变为CRC治疗提供了新的治疗点.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 不调节的RNA拼接是结直肠癌 (CRC) 的标志,但其在单细胞水平上的完整复杂性尚未得到充分理解.
- 在单个细胞中对全长的转录变异进行概括,这带来了重大的技术挑战.
研究的目的:
- 使用先进的测序技术,全面定义CRC患者结直肠上皮细胞的全长转录组.
- 调查异形多样性,拼接变化及其在结直肠癌发展中的功能后果.
主要方法:
- 在12名CRC患者的结肠直肠上皮细胞上采用高深度,长时间读取的单细胞RNA测序 (scRNA-seq).
- 进行了基因基因特异表达分析和功能验证实验.
主要成果:
- 揭示了CRC细胞中广泛的异形多样性和广泛的拼接变化,包括增加的转录复杂性,3'-UTR缩短和减少的内子保留.
- 在内在共识分子亚型 (iCMS) 中确定了不同的拼接调节模式,iCMS3显示了增强的拼接因子活性和更明显的3'-UTR缩短.
- 证明异形转移可以改变蛋白质序列,影响致癌效应,并将突变的PPIG与广泛的拼接失调联系起来.
结论:
- 结肠直肠癌表现出显著的转录基因可塑性,由改变的RNA拼接驱动.
- 突变的PPIG在调节CRC中的RNA剪接和瘤相关过程中发挥着关键作用.
- 这些发现表明,开发结直肠癌的基于拼接的治疗策略的新型候选标.
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