miR-1246 shuttling from fibroblasts promotes colorectal cancer cell migration

Cancer-associated fibroblasts (CAFs) are the major constituents of the tumor microenvironment and promote cancer development via tumor-stromal interactions. The alteration of microRNA (miRNA) expression in fibroblasts can induce the phenotype conversion between normal fibroblasts and CAFs in certain tumor types. However, the mechanisms underlying the phenotype conversion of fibroblasts in colorectal cancer (CRC) are largely unknown. Our study focuses on the role of miR-1246 in fibroblasts-CRC cells interaction. In this study, CCD-18Co colorectal fibroblasts were cultured in the conditioned medium (CM) derived from CRC cells to obtain the CAF phenotype. We found that the miR-1246 expression was upregulated in CAF-like fibroblasts compared with normal fibroblasts. miR-1246 secreted by cancer cells could be utilized by neighboring fibroblasts for CAF reprogramming. On the other hand, following secretion by CAF-like fibroblasts, miR-1246 was delivered into CRC cells and promoted cell migration via the activation of the Wnt/β-catenin signaling in CRC cells. Furthermore, high miR-1246 expression in CRC tissues was negatively associated with disease-free survival (DFS) for CRC patients. Taken together, our results reveal that miR-1246 can shuttle between CRC cells and fibroblasts. This study also indicates that targeting miR-1246 or blocking its transport from CAFs to CRC cells might represent a novel therapeutic approach in CRC treatment.