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

2019 
MicroRNA7085p (miR7085p) and epithelialtomesenchymal transition (EMT) have been widely identified to contribute to the pathogenesis and progression of multiple cancers. However, the connection between miR7085p and EMT has not been sufficiently clarified. Therefore, our research aimed to investigate the impact of miR7085p 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 miR7085p was lower in OS cells. Overexpression of miR7085p was able to impair the migration and invasion of OS cells. Moreover, miR7085p inhibited EMT of OS cells MG63 and SaOS2, wherein Ecadherin was increased, and Ncadherin, vimentin, and Snail were decreased. Semaphorin 4C (SEMA4C), mitogenactivated protein kinase kinase kinase 3 (MAP3K3), and zinc finger Eboxbinding homeobox 1 (ZEB1) were predicted as target genes of miR7085p by bioinformatics method. Only ZEB1, one of the EMTinducing transcription factors, was validated as the direct target gene of miR7085p in OS cells through dualluciferase reporter assay and Western blot analysis. Knockdown of ZEB1 was found to inhibit the metastasis of MG63 and SaOS2 cells, whereas ZEB1 over-expression promoted their metastasis. In summary, miR7085p impaired the metastasis and EMT of OS, which was found to be mediated by inhibition of ZEB1.
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