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

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

来源：Cell Death & Disease, 2021, 12(6): 576.

DOI：10.1038/s41419-021-03803-8

• COLORECTAL-CANCER
• TUMOR-GROWTH
• MICRORNA-21
• METASTASIS
• INVASION
• CELLS

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 beta-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.

• 单位
  广东医学院; 南方医科大学; 东莞市人民医院