miR-495 suppresses osteosarcoma growth and metastasis by directly targeting RUNX3 in the PI3K/Akt pathway in vitro and in vivo

Objective This study aimed to identify miR-495 as a potential regulator in osteosarcoma and characterize its role in tumor progression and underlying signaling pathways. Methods Differentially expressed miRNAs in osteosarcoma were screened from the GSE39058 dataset using bioinformatics analysis. miR-495 expression was validated in tissues/cells using S-MED database and qPCR. Functional assays, including proliferation, invasion, and apoptosis analyses, were performed following transfection with miR-495 mimics or inhibitors. Transcriptome sequencing combined with dual-luciferase assays identified RUNX3 as a direct target, and Western blot analyzed PI3K/Akt pathway activation. Results miR-495 was downregulated in osteosarcoma tissues/cells, positively correlating with patient survival. miR-495 overexpression inhibited cell proliferation, invasion, and migration, while promoting apoptosis by suppressing PI3K/Akt pathway (downregulating p-Akt, Bcl-2; upregulating Bax, c-casp3). RUNX3 overexpression rescued these effects, confirming it as a functional target. Conclusion miR-495 acts as a tumor suppressor in osteosarcoma by targeting RUNX3 to inhibit PI3K/Akt signaling, suggesting its potential as a prognostic marker and therapeutic target.