The microRNA-708-5p/ZEB1/EMT axis mediates the metastatic potential of osteosarcoma

MicroRNA-708-5p (miR-708-5p) and epithelial- to-mesenchymal transition (EMT) have been widely identified to contribute to the pathogenesis and progression of multiple cancers. However, the connection between miR-708-5p and EMT has not been sufficiently clarified. Therefore, our research aimed to investigate the impact of miR-708-5p on EMT and the metastasis of osteosarcoma (OS). We first analyzed the differentially expressed microRNAs (DEmiRNAs) from the GSE70367 dataset. We found that the expression of miR-708-5p was lower in OS cells. Overexpression of miR-708-5p was able to impair the migration and invasion of OS cells. Moreover, miR-708-5p inhibited EMT of OS cells MG63 and SaOS-2, wherein E-cadherin was increased, and N-cadherin, vimentin, and Snail were decreased. Semaphorin 4C (SEMA4C), mitogen-activated protein kinase kinase kinase 3 (MAP3K3), and zinc finger E-box-binding homeobox 1 (ZEB1) were predicted as target genes of miR-708-5p by bioinformatics method. Only ZEB1, one of the EMT-inducing transcription factors, was validated as the direct target gene of miR-708-5p in OS cells through dual-luciferase reporter assay and Western blot analysis. Knockdown of ZEB1 was found to inhibit the metastasis of MG63 and SaOS-2 cells, whereas ZEB1 overexpression promoted their metastasis. In summary, miR-708-5p impaired the metastasis and EMT of OS, which was found to be mediated by inhibition of ZEB1.