来自M2巨细胞衍生的小细胞外囊泡 (sEV) 的circFTO通过调节miR-148a-3pPDK4轴增强NSCLC恶性瘤
Qingtao Liu1, Pei Xu1, Mingming Jin2
1Department of Cardiothoracic Surgery, School of Medicine, Xinhua Hospital Affiliated Shanghai Jiao Tong University, Shanghai, 200092, People's Republic of China.
Cancer immunology, immunotherapy : CII
|March 30, 2024
概括
来自M2巨细胞的小细胞外囊中的循环RNAFTO (circFTO) 促进非小细胞肺癌 (NSCLC) 的进展和糖解. circFTO可以作为NSCLC的诊断生物标志物和治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 瘤相关巨细胞 (TAMs) 是瘤微环境 (TME) 的关键,并影响非小细胞肺癌 (NSCLC) 的进展.
- 小型细胞外囊泡 (sEVs) 和它们的载荷,包括由TAMs分泌的circRNAs,可以调节TME内的免疫反应.
- 在NSCLC中,来自M2巨细胞的sEV circRNAs的特定作用和机制在很大程度上仍未被描述.
研究的目的:
- 研究NSCLC中M2巨衍生的sEVcircRNAs的生物功能和分子机制.
- 为了确定特定的circRNAs参与NSCLC进展中介于M2巨衍生的sEVs.
- 探索这些circRNAs作为NSCLC的诊断生物标记物和治疗点的潜力.
主要方法:
- 从M2巨细胞 (M2-EVs) 中分离sEVs并评估它们对NSCLC细胞的影响.
- RNA测序以识别M0和M2-EV中差异表达的circRNAs.
- 在NSCLC组织和细胞中使用RT-qPCR和FISH验证circFTO表达.
- 功能性实验以阐明NSCLC中circFTO的机制,包括体内研究和光酶记者分析.
主要成果:
- 高通量测序揭示了M2-EVs中的circFTO丰富.
- 在NSCLC组织和细胞系中,circFTO表达显著升高,与患者存活率负相关.
- 发现circFTO针对miR-148a-3p和PDK4,调节NSCLC的扩散,迁移和糖解.
- Knockdown 的 circFTO 抑制了 in vivo 的瘤生长和转移,在调节 miR-148a-3p 或 PDK4 后恢复恶性瘤.
结论:
- 来自M2巨细胞的circFTO通过miR-148a-3p/PDK4轴促进NSCLC的进展和糖解.
- circFTO显示出作为NSCLC的预后和诊断生物标志物的潜力.
- circFTO代表了NSCLC治疗向的一个有前途的候选人.
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