由YTHDF2介导的circYAP1通过激活YAP1/TCF4-PD-L1轴驱动免疫逃生和癌症进展
Zhuang Chen1,2, Wenkang Wang3, Shengyun Hu1
1Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
循环RNAcircYAP1通过使免疫系统能够逃脱,促进结直肠癌 (CRC) 的进展. 循环YAP1的升调通过增加PD-L1来抑制CD8+T细胞活性,这表明循环YAP1是CRC的治疗点.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 免疫逃生有助于结直肠癌 (CRC) 的预后不佳.
- 循环RNAs (circRNAs) 与瘤进展和免疫逃避有关.
- 升高的circYAP1表达与CRC患者的较差结果相关.
研究的目的:
- 调查circYAP1在结直肠癌进展和免疫逃生中的作用.
- 阐明circYAP1影响瘤免疫力的分子机制.
主要方法:
- 进行了体外和体内活体功能实验.
- 机制研究包括评估circYAP1与YAP1的相互作用及其对PD-L1表达的影响.
- 对circYAP1,YAP1,TCF4和PD-L1相互作用的分析.
主要成果:
- 较高的circYAP1表达与较差的CRC预后有关.
- 循环YAP1上调抑制了通过增加PD-L1水平来抑制CD8+T细胞细胞毒性.
- CircYAP1稳定了YAP1蛋白质,促进了它的核定位.
- YAP1与TCF4相互作用,驱动CRC细胞中的PD-L1转录.
结论:
- CircYAP1通过YAP1/TCF4-PD-L1轴促进结直肠癌的免疫逃生和进展.
- 在CRC中,CircYAP1代表了组合免疫疗法的潜在治疗标.
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