miR-766-3p suppressed tumorigenesis, epithelial-mesenchymal transition, and metastasis by targeting BCL9L via β -catenin signaling pathway in osteosarcoma cells
Abstract Background Emerging evidence has indicated that abnormal microRNAs (miRNAs) play critical roles in carcinogenesis and progression of osteosarcoma (OS). The aim of this study was to clarify the relationship between miR-766-3p expression and osteosarcoma development and to explore its potential mechanism. Methods miR-766-3p was the most downregulated miRNA by analyzing GSE65071 from the GEO database. RT-PCR and western blot was performed to determine miR-766-3p expression and its specific target gene in human OS samples and cell lines. CCK-8 proliferation, colony formation, EdU, wound-healing, and transwell assays were used respectively to evaluate the influences of miR-766-3p depletion or ectopic expression on OS proliferation, migration and invasion in vitro. And a mouse tumorigenicity model was conducted to investigate effects of miR-766-3p in vivo. Moreover, we identified directly interactions between miR-766-3p and its specific target gene using luciferase reporter assays. Results miR-766-3p expression was overexpressed in OS tissues and cell lines, and ectopic miR-766-3p expression repressed the malignant level of OS, including cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT) in vitro and in vivo. B-Cell Lymphoma 9-Like Protein (BCL9L) was negatively correlated with miR-766-3p expression in human OS tissue, and was validated as a downstream target of miR-766-3p by the luciferase reporter assay and Western blotting. Rescue experiment indicated that BCL9L could restore the effects of miR-766-3p on OS migration and invasion. The β-Catenin signaling pathway was demonstrated as being implicated in the miR-766-3p/BCL9L axis. Conclusions In conclusion, miR-766-3p is a negative regulator of BCL9L and a risk factor for tumor metastasis in OS progression.