Cancer-secreted exosomal miR-21-5p induces angiogenesis and vascular permeability by targeting KRIT1

癌症分泌的外泌体 miR-21-5p 通过靶向 KRIT1 诱导血管生成和血管通透性

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作者:Qinglian He #, Aihua Ye #, Weibiao Ye, Xiaomin Liao, Guoqiang Qin, Yongqiang Xu, Yuting Yin, Huanqian Luo, Muhua Yi, Liying Xian, Shihao Zhang, Xiyuan Qin, Wei Zhu, Yuling Li

Abstract

Cancer-secreted exosomes are critical mediators of cancer-host crosstalk. In the present study, we showed the delivery of miR-21-5p from colorectal cancer (CRC) cells to endothelial cells via exosomes increased the amount of miR-21-5p in recipient cells. MiR-21-5p suppressed Krev interaction trapped protein 1 (KRIT1) in recipient HUVECs and subsequently activated β-catenin signaling pathway and increased their downstream targets VEGFa and Ccnd1, which consequently promoted angiogenesis and vascular permeability in CRC. A strong inverse correlation between miR-21-5p and KRIT1 expression levels was observed in CRC-adjacent vessels. Furthermore, miR-21-5p expression in circulating exosomes was markedly higher in CRC patients than in healthy donors. Thus, our data suggest that exosomal miR-21-5p is involved in angiogenesis and vascular permeability in CRC and may be used as a potential new therapeutic target.

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