A m6A writer RBM15 enhances the cell malignancy of osteosarcoma by mediating m6A modification of lncRNA THAP9-AS1.

Background: Osteosarcoma (OS) remains a potentially fatal disease in children. Increasing evidence highlights the implication of lncRNAs and N6-methyladenosine (m6A) modification in OS malignancies. Here, we aimed to decipher the pathological significance of RBM15-mediated m6A modification of lncRNA THAP9-AS1 in OS progression.

Methods: The expression levels of THAP9-AS1 and RBM15 in OS tissues and cell lines was determined by qRT-PCR. Based on the abnormal regulation of THAP9-AS1 and RBM15, the CCK8, colony-formation, and transwell invasion assays were used to evaluate the viability, clone formation capacity, and invasive ability of OS cells. A mouse model of tumor transplantation was utilized to ascertain the role of THAP9-AS1 silencing in vivo. The relationship between THAP9-AS1 and RBM15 was determined by RIP and MeRIP assays.

Results: THAP9-AS1 and RBM15 were significantly elevated in OS. Silencing of THAP9-AS1 or RBM15 decreased the proliferative and invasive ability of OS cells in vitro, and inhibition of THAP9-AS1 delayed the tumorous growth in vivo. Interestingly, THAP9-AS1 binds to RBM15, and was stimulated by RBM15 to promote m6A level and translation. Furthermore, THAP9-AS1 upregulation promoted OS cell invasion and survival, and this promotion of OS cell malignancy was abrogated by RBM15 silencing.

Conclusion: THAP9-AS1 serves as a tumor promoter by accelerating the malignant progression of OS by undergoing m6A modification, which is mediated by RBM15. This suggests that RBM15-m6A-THAP9-AS1 may be a potential target for OS treatment.