METTL3 upregulates COPS5 expression in osteosarcoma in an m6A-related manner to promote osteosarcoma progression.

N6-methyladenosine (m6A) is the most abundant and well-studied internal modification of messenger RNAs (mRNAs). Although m6A mRNA modification has been frequently observed in osteosarcoma, the roles and underlying mechanisms of m6A modification are not yet fully elucidated. In this study, an m6A regulator, METTL3, showed to be dramatically up-regulated within osteosarcoma tissues and cells than non-cancerous healthy samples and human normal osteoblasts, respectively. In vitro, knockdown of METTL3 suppressed the viability of osteosarcomas, and their abilities to migrate and invade; in vivo, knockdown of METTL3 repressed tumor growth within xenotransplant tumor model. METTL3 upregulates COPS5 expression may be through promoting COPS5 methylation to stabilize COPS5 mRNA. The expression level of COPS5 also showed to be up-regulated within osteosarcoma tissue samples and cells. COPS5 knockdown caused no changes in METTL3 effects on METTL3 expression but partially eliminated METTL3 effects on COPS5 expression. METTL3 overexpression promoted, whereas COPS5 knockdown inhibited the malignant behaviors of osteosarcoma cells; COPS5 knockdown partially eliminated the effects of METTL3 overexpression on osteosarcoma cells. Conclusively, METTL3 and COPS5 serve as oncogenic regulators in osteosarcoma. METTL3 upregulates COPS5 expression in osteosarcoma in an m6A-related manner.