The microRNA-4766/VEGFA axis mediates macrophage M2-type polarization to inhibit colorectal cancer proliferation and migration

To investigate the miR-4766/VEGFA axis in regulating M2-type macrophage polarization under hypoxia and its effect on the proliferation and migration of colorectal cancer (CRC) cells.The differentially expressed genes (DEGs) in macrophages before and after hypoxia treatment in the dataset GSE154427 were analyzed. microRNA (miR)-4766 and VEGFA were selected as the research objects and then detected for mRNA expression and protein level using qRT-PCR and Western blot, respectively. The expression levels of M2 macrophage markers such as CD206, CD163, and ARG1 were detected to determine the M2-type macrophage polarization. The targeted binding of miR-4766 to VEGFA was verified using Dual-luciferase reporter gene assay. CCK-8 and Transwell assays were performed, respectively, to detect the capacity of cells to proliferate and migrate. IL-10 and TGF-β levels in the conditioned medium were detected using ELISA.miR-4766 was upregulated, and VEGFA was downregulated in hypoxia-treated macrophages. miR-4766 inhibited, while VEGFA promoted the polarization of M2-type macrophages. miR-4766 targeted and negatively regulated VEGFA. miR-4766 inhibited the polarization of M2-type macrophages and then suppressed CRC cell proliferation and migration via targeting VEGFA.Restoring miR-4766 expression to inhibit VEGFA expression promised to be a potential strategy to suppress CRC development.