Downregulation of microRNA-660 inhibits cell proliferation and invasion in osteosarcoma by directly targeting forkhead box O1

Abstract

The abnormal expression of microRNAs (miRNAs/miRs) has been observed in osteosarcoma (OS), and these differently expressed miRNAs contribute to the occurrence and development of OS by regulating various biological behaviours. Therefore, a comprehensive understanding of the detailed roles of aberrantly expressed miRNAs in OS progression may be favourable to the identification of promising therapeutic strategies for the treatment of patients with this malignancy. The present study demonstrated that miR-660-5p (miR-660) expression was significantly upregulated in OS tissues and cell lines compared with that in normal adjacent tissues and normal human osteoblast hFOB1.19, respectively. miR-660 downregulation led to a significant decrease in the proliferation and invasion of OS cells. Forkhead box O1 (FOXO1) was predicted as a potential target of miR-660. The subsequent luciferase reporter assay indicated that miR-660 directly binds to the 3'-untranslated region of FOXO1. Furthermore, miR-660 inhibition increased the FOXO1 expression in OS cells at mRNA and protein levels. Moreover, FOXO1 was downregulated in OS tissues and this downregulation was negatively correlated with miR-660 levels. Besides, rescue experiments demonstrated that FOXO1 knockdown abolished the effects of miR-660 knockdown on OS cell proliferation and invasion. These results suggest that miR-660 may serve oncogenic roles in OS by directly targeting FOXO1. Targeting miR-660 may be an effective candidate for the treatment of patients with OS.