Nuclear apoptosis‐inducing factor 1 (NAIF1) acts as an oncogene and involves in tumorigenesis in several cancers. However, the expression and mechanism of NAIF1 in osteosarcoma remains unclear. In this study, we demonstrated the downregulation of NAIF1 expression in both osteosarcoma tissues and cell lines. We next explored the potential role of NAIF1 in osteosarcoma cell proliferation and migration. The result showed that overexpression of NAIF1 evidently suppressed the cell proliferation and invasion of osteosarcoma. Furthermore, we investigated the potential mechanisms accounting for dysregulation of NAIF1 in osteosarcoma. The bioinformatic prediction and luciferase reporter assay revealed that miR‐128 is a direct upstream regulator of NAIF1 and regulates NAIF1 expression by binding the 3′‐UTR of NAIF1. Consistent with previous study, we found that miR‐128 was upregulated in both osteosarcoma tissues and cell lines. Moreover, miR‐128 expression levels were inversely correlated with that of NAIF1 in osteosarcoma tissues. Finally, functional assay showed that miR‐128 significantly suppressed osteosarcoma progression partially mediated by inhibiting NAIF1 expression. These data ind
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