Abstract
Metastasis is the leading cause of colorectal cancer treatment failure and mortality. Communication between endothelium and tumor cells in the tumor microenvironment is required for cancer metastasis. Tumor-derived exosomes have been shown to increase vascular permeability by delivering microRNA (miRNA) to vascular endothelial cells, facilitating cancer metastasis. The mechanism by which Epithelial-mesenchymal transition (EMT) tumor cell-derived exosomes influence vascular permeability remains unknown. MicroRNA-29a (miR-29a) expression is up-regulated in colorectal cancer (CRC) tissues, which is clinically significant in metastasis. Exosomal miR-29a secreted by EMT-CRC cells has been found to decrease the expression of Zonula occlusion 1 (ZO-1), Claudin-5, and Occludin via targeting Kruppel-like factor 4 (KLF4). In vitro co-culture investigations further revealed that EMT-cancer cells release exosomal miR-29a, which alters vascular endothelial permeability. Furthermore, exosomal miR-29a promoted liver metastases in CRC mice. Our findings demonstrate that EMT-CRC cells may transport exosomal miR-29a to endothelial cells in the tumor microenvironment (TME). As a result, increased vascular permeability promotes the development and metastasis of CRC. Exosomal miR-29a has the potential to be a predictive marker for tumor metastasis as well as a viable therapeutic target for CRC.