Cancer-derived exosomal miR-25-3p promotes pre-metastatic niche formation by inducing vascular permeability and angiogenesis
Cancer-derived exosomal miR-25-3p promotes pre-metastatic niche formation by inducing vascular permeability and angiogenesis
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癌症来源的外泌体 miR-25-3p 通过诱导血管通透性和血管生成促进转移前生态位形成
DOI：
10.1038/s41467-018-07810-w
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发表时间：
2018-12-19
影响因子：
16.6
通讯作者：
Liang, Li
中科院分区：
文献类型：
--
作者：
Zeng, Zhicheng;Li, Yuling;Liang, Li
癌症来源的外切体被认为是在外国部位癌症诱导的转移前生态位形成的主要驱动力，但其机制尚不清楚。在这里，我们证明了miR-25-3p，一种促进结直肠癌转移的miRNA，可以通过外切体从结直肠癌细胞转移到内皮细胞。外体miR-25-3p通过靶向KLF2和KLF4调节血管内皮细胞VEGFR2、ZO-1、occludin和Claudin5的表达，从而促进血管通透性和血管生成。此外，结直肠癌细胞外体miR-25-3p可显著诱导血管渗漏，促进小鼠肝、肺结直肠癌的转移。此外，有转移的大肠癌患者外周血中miR-25-3p的表达水平明显高于无转移的患者。我们的工作表明，外体miR-25-3p参与了转移前生态位的形成，并可能作为结直肠癌转移的血液生物标志物。
Cancer-derived exosomes are considered a major driver of cancer-induced pre-metastatic niche formation at foreign sites, but the mechanisms remain unclear. Here, we show that miR-25-3p, a metastasis-promoting miRNA of colorectal cancer (CRC), can be transferred from CRC cells to endothelial cells via exosomes. Exosomal miR-25-3p regulates the expression of VEGFR2, ZO-1, occludin and Claudin5 in endothelial cells by targeting KLF2 and KLF4, consequently promotes vascular permeability and angiogenesis. In addition, exosomal miR-25-3p from CRC cells dramatically induces vascular leakiness and enhances CRC metastasis in liver and lung of mice. Moreover, the expression level of miR-25-3p from circulating exosomes is significantly higher in CRC patients with metastasis than those without metastasis. Our work suggests that exosomal miR-25-3p is involved in pre-metastatic niche formation and may be used as a blood-based biomarker for CRC metastasis.