MicroRNAs (miRNAs) are endogenous, non-coding, small RNAs, which play a critical role in regulating varieties of the biological and pathologic processes. Several reports have indicated that miR-370 acts as a tumor suppressor in varieties of tumors. However, the roles of miR-370 in osteosarcoma have not been reported. In this study, our objective was to explore the biological functions and its molecular mechanism of miR-370 in osteosarcoma cell lines, finding a therapeutic target of osteosarcoma. Our data demonstrated that miR-370 was evidently reduced in osteosarcoma cell lines, whereas FOXM1 expression was markedly increased. Up-regulation of miR-370 suppressed proliferation, arrested cell cycle and induced apoptosis in osteosarcoma cells. Besides, invasion and EMT of osteosarcoma cells was also inhibited by introduction of miR-370. Next, we found that FOXM1 expression was significantly reduced by up-regulation of miR-370. Bioinformatics analysis predicted that the FOXM1 was a potential target gene of miR-370. Luciferase reporter assay further confirmed that miR-370 could directly target the 3' UTR of FOXM1. Overexpression of FOXM1 in osteosarcoma cells transfected with miR-370 mimic partially reversed the effects of miR-370. In conclusion, miR-370 inhibited cell growth and metastasis in osteosarcoma cells by down-regulation of FOXM1.
Keywords: EMT; FOXM1; Osteosarcoma; invasion; miR-370; proliferation.