RBM15-mediated ASPM m6A modification facilitates osteosarcoma progression via IGF2BP3-dependent manner

Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, with limited improvement in survival for patients with metastatic or recurrent disease. RBM15 is an important N6-methyladenosine (m 6 A) writer; however, its role in OS remains incompletely understood. This study aimed to investigate the role of abnormal spindle microtubule assembly (ASPM) in OS progression and its regulation by RBM15-mediated m 6 A modification. Differentially expressed genes in OS were identified using a GEO dataset. The functional role of ASPM was evaluated using in vitro assays. The relationships among ASPM, RBM15, and IGF2BP3 were analyzed by RT-qPCR, Western blot, MeRIP, mRNA stability, and RIP assays. Rescue experiments and mouse xenograft models were performed to assess the functional contribution of the RBM15/ASPM axis to OS malignant phenotypes. Bioinformatic analyses identified ASPM as a potential downstream target of RBM15 in OS. ASPM silencing inhibited OS cell proliferation, migration, and invasion. RBM15 overexpression increased ASPM mRNA and protein levels and enhanced its mRNA stability in an m 6 A-dependent manner. Furthermore, the m 6 A reader IGF2BP3 recognized ASPM transcripts and contributed to ASPM stability. Functionally, RBM15 silencing partially reversed the promotive effects of ASPM overexpression, supporting a role for ASPM in mediating OS malignancy. This study identifies a novel RBM15/m 6 A/ASPM/IGF2BP3 regulatory axis in OS and provides evidence that m 6 A-dependent RNA stabilization contributes to tumor progression. These findings offer potential insights into epitranscriptomic regulation and suggest possible therapeutic targets for OS.