Abstract
Gastric cancer (GC), a malignant tumor, is highly prevalent, particularly in Asia. miR-509-3p plays a crucial role in regulating tumorigenesis, but its mechanism in GC remains unclear. Potential targets of miR-509-3p were identified through database analyses (miRWalk, TargetScan, ENCORI, and TCGA). The binding site between miR-509-3p and forkhead box protein M1 (FOXM1) was confirmed using a dual-luciferase assay. CCK-8, EdU, Transwell, wound healing assays, flow cytometry, and Western blot analysis were employed to examine changes in proliferation, migration, invasion, apoptosis, FOXM1, and the p38 MAPK (p38)/MAPK-activated protein kinase 2 (MK2) pathway in GC cells (MNK-45 and HGC-27) after miR-509-3p overexpression or knockdown, FOXM1 overexpression, and application of the p38 pathway agonist Anisomycin. The size and weight of subcutaneous xenografts were measured, and the effects of miR-509-3p overexpression were analyzed through histopathological staining (Tunel immunofluorescence, HE staining, Ki67, and FOXM1 immunohistochemistry). The results showed that overexpression of miR-509-3p suppressed proliferation, migration, and invasion, while accelerating apoptosis. Knockdown of miR-509-3p promoted malignant progression. miR-509-3p inhibited GC by regulating FOXM1-mediated p38/MK2 pathway activation, and miR-509-3p mimics restrained tumor growth in vivo through this pathway. In conclusion, miR-509-3p suppresses GC malignant progression by regulating FOXM1-mediated p38/MK2 pathway activation.