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

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: Restoring miR-4766 expression to inhibit VEGFA expression promised to be a potential strategy to suppress CRC development.

Keywords: Colorectal cancer; Macrophage polarization; MicroRNA-4766; Migration; Proliferation; VEGFA.