癌细胞分泌的细胞外囊泡向p53准,以损害肌肉中的线粒体功能
Xianhui Ruan1, Minghui Cao1, Wei Yan1
1Department of Pathology, University of California San Diego, La Jolla, CA, USA.
EMBO reports
|July 13, 2023
概括
乳腺癌细胞释放出细胞外囊泡,通过损害线粒体,导致骨肌肉衰弱. 这涉及转移microRNA-122-5p,它针对TP53,破坏线粒体功能和肌肉细胞的能量生产.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
背景情况:
- 骨肌的损失和软弱会对癌症患者的预后和生活质量产生负面影响.
- 众所周知,瘤衍生因素会诱导肌肉消耗 (缓解症) 和细胞死亡 (细胞亡).
研究的目的:
- 研究乳腺癌细胞中的细胞外囊泡 (EV) 在骨肌肉功能障碍中的作用.
- 阐明癌症EVs影响肌肉线粒体的分子机制.
主要方法:
- 对暴露于癌症EVs的骨肌中线粒体含量,功能和氧化应激的分析.
- 从癌症EV转移到肌肉细胞 (肌细胞) 的微RNA转移的特征.
- 研究TP53 (瘤抑制剂) 和其在肌肉细胞中的下游点.
主要成果:
- 乳腺癌细胞分泌的EVs降低了线粒体含量,能量生产,并增加了骨肌肉中的氧化应激.
- 在EVs中的miR-122-5p转移到肌细胞,准TP53并降低关键的线粒体基因 (Tfam,Pgc-1α,Sco2,16SrRNA).
- 在肌肉中恢复TP53改善了线粒体问题,并在携带瘤的小鼠中部分改善了跑步能力.
结论:
- 来自乳腺癌细胞的细胞外囊泡介导骨肌肉线粒体功能障碍.
- 这种EV介导的机制有助于在一些癌症患者中观察到的肌肉衰弱.
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