Metformin promotes apoptosis in colorectal cancer through the miR-211-5p/MMP9 pathway

Background and Aims Recent studies have shown that metformin can positively affect colorectal cancer (CRC) prevention and treatment. This study investigated whether metformin exerts its antitumor effects by modulating the miR-211-5p/MMP9 axis in CRC cells. Methods SW480 and SW620 CRC lines were treated with 5 mM metformin for 48 h, and the experimental groups consisted of metformin-treated and untreated control cells. Cell viability, apoptosis, migration, and protein expression were evaluated using Cell Counting Kit-8 (CCK-8), flow cytometry, wound healing assay, and western blot analysis, respectively. The expression levels of miR-211-5p and MMP9 were determined by quantitative real-time PCR (qRT-PCR). Gain- and loss-of-function experiments were performed using miR-211-5p mimic and inhibitor, and a dual-luciferase reporter assay was conducted to validate MMP9 as a direct target of miR-211-5p . Differences between the two groups were analyzed using Student’s t-test, while comparisons among multiple groups were conducted using one-way analysis of variance (ANOVA). Results Metformin significantly reduced cell viability and induced apoptosis in both SW480 and SW620 cells. It upregulated the expression of miR-211-5p while suppressing MMP9 at both the mRNA and protein levels. Luciferase reporter assay confirmed that MMP9 is a direct target of miR-211-5p . Overexpression of miR-211-5p further enhanced the antiproliferative and pro-apoptotic effects of metformin. Moreover, the combined treatment with metformin and miR-211-5p mimic markedly inhibited CRC cell migration compared with either treatment alone. Conclusion Metformin suppresses colorectal cancer progression by modulating the miR-211-5p/MMP9 axis, resulting in reduced cell viability, enhanced apoptosis, and impaired cell migration. These findings suggest that the miR-211-5p/MMP9 axis may contribute to the anticancer effects of metformin.