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

ABSTRACT: 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 over-expression 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.

SUBMITTER: Feng T 

PROVIDER: S-EPMC6967104 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature