Abstract

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.