Cancer-derived exosomal miR-25-3p promotes pre-metastatic niche formation by inducing vascular permeability and angiogenesis

Zhicheng Zeng, Yuling Li, Yangjian Pan, Xiaoliang Lan, Fuyao Song, Jingbo Sun, Kun Zhou, Xiaolong Liu, Xiaoli Ren, Feifei Wang, Jinlong Hu, Xiaohui Zhu, Wei Yang, Wenting Liao, Guoxin Li, Yanqing Ding and Li Liang ()
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Zhicheng Zeng: Nanfang Hospital, Southern Medical University
Yuling Li: Southern Medical University
Yangjian Pan: The Third Affiliated Hospital of Southern Medical University
Xiaoliang Lan: Southern Medical University
Fuyao Song: Nanfang Hospital, Southern Medical University
Jingbo Sun: The Third Affiliated Hospital of Southern Medical University
Kun Zhou: The Third Affiliated Hospital of Southern Medical University
Xiaolong Liu: The Third Affiliated Hospital of Southern Medical University
Xiaoli Ren: Nanfang Hospital, Southern Medical University
Feifei Wang: Nanfang Hospital, Southern Medical University
Jinlong Hu: Nanfang Hospital, Southern Medical University
Xiaohui Zhu: Nanfang Hospital, Southern Medical University
Wei Yang: Nanfang Hospital, Southern Medical University
Wenting Liao: Nanfang Hospital, Southern Medical University
Guoxin Li: Southern Medical University
Yanqing Ding: Nanfang Hospital, Southern Medical University
Li Liang: Nanfang Hospital, Southern Medical University

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-07810-w

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