Exosomal miR-224-5p from colorectal cancer cells promotes malignant transformation of human colon normal cells by promoting cell proliferation through downregulation of CMTM4

Abstract

Background Interactions between malignant cells and neighboring normal cells is important for carcinogenesis. In addition, cancer cell-derived exosomes have been shown to promote the malignant transformation of recipient cells, but the mechanisms remain unclear. Methods The level of miR-224-5p in colorectal cancer (CRC) cell-derived exosomes was determined by RT-qPCR assay. In addition, PKH26 dye-labeled exosomes were used to assess the efficacy of the transfer of exosomes between SW620 and CCD 841 CoN cells. Results In this study, we found that overexpression of miR-224-5p significantly promoted the proliferation, migration and invasion of SW620 cells. In addition, miR-224-5p can be transferred from SW620 cells to CCD 841 CoN cells via exosomes. SW620 cell-derived exosomes overexpressing miR-224-5p markedly promoted proliferation, migration and invasion of CCD 841 CoN cells. Meanwhile, SW620 cell-derived exosomal miR-224-5p notably decreased the expression of CMTM4 in CCD 841 CoN cells. Furthermore, SW620 cell-derived exosomal miR-224-5p significantly inhibited tumor growth in a xenograft model in vivo. Conclusion These findings suggested that SW620 cell-derived exosomal miR-224-5p could promote malignant transformation and tumorigenesis in vitro and in vivo via downregulation of CMTM4, suggesting that miR-224-5p might be a potential target for therapies in CRC.