The expression and function of miRNA-451 in osteosarcoma.

MicroRNA-451 has been proven down-regulated in many human malignancies and correlated with tumor progression. However, its expression and clinical significance in osteosarcoma is still unclear. Thus, the aim of this study was to explore the effects of miR-451 in osteosarcoma tumorigenesis and development. The expression level of miR-451 was quantified by quantitative real-time reverse-transcriptase-polymerase chain reaction in primary osteosarcoma tissues and osteosarcoma cell lines. MTT, flow cytometric, and scratch migration assay were used to test the proliferation, apoptosis, and migration of miR-451 transfection osteosarcoma cells, and a mouse model was used to investigate tumorigenesis. The expression levels of miR-451 in osteosarcoma tissues were significantly lower than those in corresponding noncancerous bone tissues (P < 0.001). In addition, miR-451 down-regulation more frequently occurred in osteosarcoma specimens with advanced clinical stage (P < 0.001), positive distant metastasis (P = 0.015), and poor response to neoadjuvant chemotherapy (P < 0.001). Univariate and multivariate analysis identified low miR-451 expression as an unfavorable prognostic factor for both overall and disease-free survival. After miR-451 transfection, cell proliferation, migration, and tumorigenesis in the osteosarcoma cells were significantly inhibited and cell apoptosis was increased. These findings indicate that miR-451 may act not only as a novel diagnostic and prognostic marker, but also as a potential target for molecular therapy of osteosarcoma.