Let-7i inhibits the malignant phenotype of osteosarcoma cells by targeting Aurora-B

Abstract

Our previous study indicated that Aurora-B is involved in osteosarcoma (OS) cell invasion and metastasis; however, the mechanism underlying Aurora-B overexpression in OS remains unknown. In the present study, significantly downregulated let-7i expression in OS tissues and OS cells was observed compared with that in normal adjacent tumorous tissues and human osteoblast cell lines. Bioinformatic predictions have revealed a conserved binding site in a microRNA locus on Aurora-B, suggesting the potential of let-7i targeting the Aurora-B gene. To validate this, a luciferase reporter assay was performed on OS cells. The results indicated that Aurora-B is a likely to be a direct target negatively regulated by let-7i. The expression of let-7i in OS cells was restored by infection with let-7i mimics. Results revealed that Aurora-B mRNA and protein expression levels were significantly decreased. Furthermore, the proliferation, migration and invasion abilities of OS cells were significantly suppressed by infection with let-7i mimics. Notably, the inhibitory effect of silencing Aurora-B by LV-shAurora-B on cell proliferation, migratory and invasive ability was significantly lower than that by let-7i mimics, which indicated that let-7i inhibits cell malignant phenotypes partially by targeting Aurora-B in OS cells. All data suggested that let-7i may be a novel potential target for OS treatment.