为了研究miR-4766/VEGFA轴在缺氧条件下调节M2型巨噬细胞极化以及其对结直肠癌（CRC）细胞增殖和迁移的影响，分析了GSE154427数据集中巨噬细胞经过缺氧处理前后的差异表达基因（DEGs）。选择microRNA（miR）-4766和VEGFA作为研究对象，分别使用qRT-PCR和Western blot检测其mRNA表达和蛋白水平。检测了CD206、CD163和ARG1等M2型巨噬细胞标志物的表达水平，以确定M2型巨噬细胞的极化程度。使用双荧光素酶报告基因实验验证了miR-4766与VEGFA的靶向结合。分别使用CCK-8检测细胞的增殖能力和Transwell实验检测细胞的迁移能力。使用ELISA检测了培养基中的IL-10和TGF-β水平。缺氧处理的巨噬细胞中miR-4766上调，VEGFA下调。miR-4766抑制，VEGFA促进M2型巨噬细胞的极化。miR-4766靶向并负调节VEGFA。miR-4766抑制M2型巨噬细胞的极化，从而通过靶向VEGFA抑制CRC细胞的增殖和迁移。恢复miR-4766的表达以抑制VEGFA的表达被认为是抑制CRC发展的潜在策略。版权所有 © 2023 Elsevier GmbH出版

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.Copyright © 2023. Published by Elsevier GmbH.