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

• DOI: 10.1038/s41467-018-07810-w
• Publication Date: 2018-12-13T16:10:03Z
• Authors: 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; Li Liang
• Keywords: 0301 basic medicine; Neovascularization, Pathologic; Science; Q; Kruppel-Like Transcription Factors; Endothelial Cells; Mice, Nude; Exosomes; HCT116 Cells; Article; 3. Good health; Capillary Permeability; Gene Expression Regulation, Neoplastic; Kruppel-Like Factor 4; MicroRNAs; 03 medical and health sciences; HEK293 Cells; Biomarkers, Tumor; Human Umbilical Vein Endothelial Cells; Tumor Microenvironment; Animals; Humans; Neoplasm Metastasis; Colorectal Neoplasms

AbstractCancer-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.