Abstract

BACKGROUND: The aim of this study was to clarify the biological function of microRNA-449b-5p in the progression of osteosarcoma (OS) and to define the underlying mechanism.

MATERIAL AND METHODS: Relative levels of microRNA-449b-5p in OS tissues and cell lines was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between microRNA-449b-5p level and pathological characteristics of OS patients was analyzed by chi-square test. Kaplan-Meier analysis was used for survival analysis of OS patients based on their expression level of microRNA-449b-5p. Regulatory effects of microRNA-449b-5p on cellular behaviors of OS cells were evaluated by cell counting kit-8 (CCK-8) and Transwell assay. The binding relationship between microRNA-449b-5p and c-Met was verified through dual-luciferase reporter gene assay, and their interaction in OS progression was further examined through a series of rescue experiments.

RESULTS: MicroRNA-449b-5p was expressed at low levels in OS. Lower levels of microRNA-449b-5p were seen in OS tissues with worse tumor grade or histological differentiation. OS patients with low levels of microRNA-449b-5p had worse overall survival relative to those with high level of microRNA-449b-5p. Overexpression of microRNA-449b-5p markedly attenuated proliferative, migratory, and invasive abilities of OS cells. C-Met is the downstream target of microRNA-449b-5p, and its level was inhibited in OS cells overexpressing microRNA-449b-5p. Importantly, c-Met partially rescued the inhibitory effects of microRNA-449b-5p on behavior of OS cells.

CONCLUSIONS: MicroRNA-449b-5p is downregulated in OS, which alleviates the malignant progression of OS by targeting c-Met.

Keywords: MicroRNAs, Osteosarcoma, Bone Neoplasms, Disease Progression, Kaplan-Meier Estimate, Neoplasm Invasiveness, Proto-Oncogene Proteins c-met, young adult