Prognostic Value of <scp>microRNA</scp> ‐648 in Osteosarcoma and Its Regulatory Effect on Tumor Progression

The present investigation was designed to assess the prognostic value of microRNA-648 (miR-648) in osteosarcoma (OS) and elucidate its regulatory mechanisms. Quantitative real-time PCR was employed to measure miR-648 expression levels in 80 paired OS specimens and their matched adjacent non-tumor tissues. Statistical assessments of clinical parameters were conducted using Chi-squared tests, while patient survival data were evaluated through Kaplan-Meier estimation and Cox proportional hazards regression modeling. Functional assays were performed in OS cell lines. Bioinformatic prediction of target genes was followed by experimental validation using dual-luciferase reporter assays. MiR-648 exhibited significant downregulation in OS clinical specimens and cell lines (p < 0.001). Low miR-648 expression correlated with lung metastasis (p = 0.027), advanced Enneking stage (p = 0.031), and poorer progression-free survival (p < 0.001). MiR-648 was identified as a significant independent prognostic indicator (hazard ratio [HR] = 0.235, p < 0.001). Moreover, the overexpression of miR-648 significantly suppressed cellular proliferation, migration capacity, and invasion potential while enhancing apoptotic activity (p < 0.001). High mobility group box 1 (HMGB1) was confirmed as a direct target, with its role in reversing miR-648's tumor-suppressive effects. MiR-648 exerts tumor-suppressive effects in OS by modulating HMGB1, suggesting its clinical utility as both a prognostic biomarker and a therapeutic intervention point.