Exosome-mediated miR-200b promotes colorectal cancer proliferation upon TGF-β1 exposure

Exosome are emerging mediators of intercellular communication. Cancer-secreted exosome has an effect on the exosome donor cells and support cancer growth and metastasis. Here, we examine the TGF-beta 1, a multifunctional cytokine involved in the regulation of cellular signaling pathways in human cancers, significantly contributes to upregulate miR-200b in exosome from colorectal cancer cell lines. The miR-200b enriched in exosome can be transferred into a new target cell to facilitating the colorectal cancer cells proliferation. Further studies showing that the exosomal miR-200b could directly target 3'-UTRs of p27 and RND3 resulted in knockdown of respective target proteins in recipient cells. Remarkably, the overexpression of p27/kip1 in HCT-116 cell, not RND3, resulted in effectively inhibited cell proliferation which induced by exosomal miR-200b. Moreover, animal experiment studies also confirmed a stimulating effect of exosomal miR-200b on colorectal cancer cell-derived xenografts. The expression p27/kip1 have decreased in tumors xenografts after injected with exosomal miR-200b. Our observations offer an evidence that whereby exosomal specific miRNA could amplify the proliferative element into the neighboring or distant cells to effective tumor growth.