MicroRNA-625 targets Yes-associated protein 1 to suppress cell proliferation and invasion of osteosarcoma

Abstract

Osteosarcoma (OS) is the leading cause of cancer-associated mortality in adolescents and children. MicroRNAs (miRNAs) have critical roles in cancer, particularly in the initiation and progression of OS. Therefore, OS-associated miRNAs should be identified for use as therapeutic targets for treatment of OS. This study aimed to investigate the expression pattern, potential roles and underlying mechanism of microRNA-625 (miR-625) in OS. miR-625 was markedly downregulated in OS tissues and cell lines compared with that in associated adjacent non-tumor tissues and human normal osteoblasts, respectively. The enforced expression of miR-625 using miRNA mimics significantly reduced the proliferation and invasion of OS cells. Bioinformatics analysis and luciferase reporter assays indicated that miR-625 targeted the 3'-untranslated region of Yes-associated protein 1 (YAP-1). Furthermore, upregulation of miR-625 reduced endogenous YAP1 expression at the mRNA and protein levels. The upregulated expression of YAP1 in OS tissues was inversely correlated with miR-625 expression. YAP1 restoration using a recombinant plasmid rescued the miR-625-mediated tumor-suppressive effects in OS cells. In conclusion, miR-625 attenuated the cell proliferation and invasion of OS by suppressing YAP1. Thus, miR-625 may be a potential target for OS therapy.