Exosomal circVANGL1 Enhances Cisplatin Resistance in Osteosarcoma Cells by Regulating the miR-145-5p/E2F3 Axis

Background and Objectives: osteosarcoma (OS) is a malignant bone tumor originating directly from bone tissue, predominantly affecting adolescents. Cisplatin (DDP)-based chemotherapy is commonly used in the treatment of OS, but the emergence of DDP resistance poses a significant challenge to effective management. The study aimed to investigate the role of circRNA VANGL1 (circVANGL1) in mediating DDP resistance in OS. Materials and Methods the OS cell lines U2OS and MG-63 were used, and DDP-resistant cell models (U2OS-DR and MG-63-DR) were established. Transfection with circVANGL1 siRNA was performed to silence circVANGL1 expression, and its impact on cell proliferation, apoptosis, DDP resistance, and miR-145-5p level was studied. Fluorescence in situ hybridization was employed to localize circVANGL1. TargetScan prediction was utilized to identify the interaction between circVANGL1 and miR-145-5p. Co-transfection experiments of si-circVANGL1 with anti-miR-145-5p or E2F3 overexpression vector (E2F3-oe) were conducted to assess their effects on DDP-resistant cells. Results circVANGL1 expression was greatly elevated in U2OS-DR and MG-63-DR cells. Transfection with si-circVANGL1 effectively suppressed cell proliferation and DDP resistance while promoting apoptosis in DDP-resistant cells. circVANGL1 is transferred via exosomes and primarily localized in the cytoplasm of U2OS and MG-63 cells. TargetScan prediction indicated a target relationship between circVANGL1 and miR-145-5p. Co-transfection of si-circVANGL1 with anti-miR-145-5p or E2F3-oe counteracted the changes in proliferation and apoptosis observed with si-circVANGL1 transfection alone in DDP-resistant cells. Conclusion Exosomal circVANGL1 contributes to DDP resistance in OS cells via modulation of miR-145-5p/E2F3 axis.