MicroRNA-939-5p directly targets IGF-1R to inhibit the aggressive phenotypes of osteosarcoma through deactivating the PI3K/Akt pathway

Abstract

The dysregulation of microRNA-939-5p (miR-939) is involved in the development of multiple types of human cancer. However, the expression and roles of miR-939 in osteosarcoma (OS) have yet to be clarified. The expression level of miR-939 in OS was measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR). A Cell Counting Kit-8 assay, flow cytometry analysis, Transwell migration and invasion assays, and a tumor xenograft assay were employed to explore the effects of miR-939 in OS cells. Bioinformatics analysis, RT-qPCR, western blot analysis and luciferase reporter assays were performed to explore its underlying mechanism. Expression of miR-939 was decreased in both OS tissues and cell lines. The decreased miR-939 expression was notably correlated with clinical stage and distant metastasis in patients with OS, where low miR-939 levels were correlated with lower overall survival. miR-939 overexpression decreased OS cell proliferation, migration and invasion in vitro; induced cell apoptosis, and impaired tumor growth in vivo. Mechanistically, insulin-like growth factor 1 receptor (IGF-1R) was characterized as direct target gene of miR-939 in OS. The tumor-suppressing effects of miR-939 in OS cells were imitated by IGF-1R knockdown. In addition, exogenous IGF-1R expression abolished the tumor suppressive roles of miR-939 in OS cells. miR-939 was implicated in the deactivation of the PI3K/Akt pathway in OS in vitro and in vivo through regulating IGF-1R expression. The present study demonstrated that miR-939 exerted tumor-suppressing roles in the malignancy of OS cells by directly targeting IGF-1R and inactivating the PI3K/AKT pathway. Therefore, this miRNA may be a promising target for anticancer therapy in patients with OS.