Exosomal miR-92a-3p modulates M2 macrophage polarization in colorectal cancer: implications for tumor migration and angiogenesis.

Abstract

Colorectal cancer (CRC) is one of the most prevalent malignant neoplasms globally. Its development and metastasis are closely associated with the polarization of macrophages within the tumor microenvironment (TME). In particular, the polarization of M2-type macrophages has been demonstrated to be related to the promotion of tumor growth, migration, and angiogenesis. This study aims to investigate the role of miR-92a-3p in colon cancer-derived exosomes in regulating M2-type macrophage polarization by targeting EID2B and to elucidate the impact of this process on tumor migration and angiogenesis. MicroRNAs that were differentially expressed in plasma exosomes from CRC patients were initially identified through a search of the GEO database. The results were then verified by RT-qPCR using miR-92a-3p. The uptake of exosomes was observed via laser confocal microscopy, and the impact of miR-92a-3p on the polarization of exosomes and macrophages was examined through the use of RT-qPCR and WB. A bioinformatics analysis and a dual-luciferase reporter assay were employed to identify the downstream target of miR-92a-3p and to investigate its effect on the MAPK/ERK pathway. miR-92a-3p was upregulated in plasma exosomes of colon cancer patients and exhibited a positive correlation with lymph node metastasis. The results demonstrated that miR-92a-3p was capable of promoting M0 macrophage polarization toward the M2 phenotype, and of enhancing the migratory and invasive capacities of CRC cells, as well as their angiogenic potential in vitro. Bioinformatic analysis and experimental validation demonstrated that miR-92a-3p targeted EID2B and that this target gene was negatively correlated with M2-type macrophage polarization. The results demonstrated that miR-92a-3p promotes macrophage M2 polarization by activating the MAPK/ERK pathway. miR-92a-3p activates the MAPK/ERK pathway and induces macrophage M2 polarization by targeting EID2B, thereby promoting migration and angiogenesis in CRC. These findings offer new potential targets for the treatment of colon cancer.