MicroRNA-944 targets vascular endothelial growth factor to inhibit cell proliferation and invasion in osteosarcoma

摘要

Emerging evidence has demonstrated that the dysregulation of microRNA (miRNA/miR) serves a crucial role in the tumorigenesis and tumor development of osteosarcoma (OS), primarily by affecting various pathological behaviors. Therefore, better knowledge of miRNA in OS may provide novel insights into the pathogenesis of OS, and may facilitate the development of promising therapeutics for patients with this disease. MiRNA-944 is frequently dysregulated in human cancers. However, the expression levels, functions and underlying mechanisms of miR-944 in OS remain largely elusive. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect miR-944 expression in OS tissues and cell lines. The regulatory influence of miR-944 in OS proliferation and invasion was determined with MTT and Transwell invasion assays. In addition, the mechanisms underlying the action of miR-944 in OS cells were elucidated through a series of experiments, including bioinformatics analysis, luciferase reporter assay, RT-qPCR and western blot analysis. Spearman's correlation analysis was utilized to examine the relationship between miR-944 and VEGF expression levels, and rescue experiments were applied to further verify whether VEGF mediates the role of miR-944 in OS. The results demonstrated that miR-944 was downregulated in cancer tissues and cell lines. Furthermore, exogenous miR-944 expression inhibited cell proliferation and invasion in OS in vitro. Vascular endothelial growth factor (VEGF) was identified as a direct target of miR-944 in OS and was overexpressed in cancer tissues. VEGF expression was inversely correlated with miR-944 expression in cancer tissues. Rescue experiments demonstrated that overexpression of VEGF partially prevented the miR-944-induced inhibition of OS cell proliferation and invasion. These results suggested that miR-944 may serve a tumor suppressive role in OS by directly targeting VEGF. Therefore, miR-944 may be a promising target in the treatment of OS.