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

Zhicheng ZengDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of ChinaYuling LiDepartment of Pathology, Dongguan People's hospital, Dongguan, Guangdong Province, People's Republic of ChinaYangjian PanDepartment of General Surgery, The Third Affiliated Hospital of Southern Medical University, Guangdong Province, People's Republic of ChinaXiao-Liang LanDepartment of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of ChinaFuyao SongDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of ChinaJingbo SunDepartment of General Surgery, The Third Affiliated Hospital of Southern Medical University, Guangdong Province, People's Republic of ChinaKun ZhouDepartment of General Surgery, The Third Affiliated Hospital of Southern Medical University, Guangdong Province, People's Republic of ChinaXiaolong LiuDepartment of General Surgery, The Third Affiliated Hospital of Southern Medical University, Guangdong Province, People's Republic of ChinaXiaoli RenDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of ChinaFeifei WangDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of ChinaJinlong HuDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of ChinaXiaohui ZhuDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of ChinaWei YangDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of ChinaWenting LiaoDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of ChinaGuoxin LiDepartment of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of ChinaYanqing DingDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of ChinaLiang LiDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of China. [email protected]

2018en

ABI

Annotatsiya

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.

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DOI: 10.1038/s41467-018-07810-w

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