Ovol2 induces mesenchymal–epithelial transition via targeting ZEB1 in osteosarcoma

PURPOSE: Osteosarcoma (OS) is the most common type of primary solid bone tumor. Ovo-like zinc finger 2 (Ovol2), a zinc finger transcription factor, is a mesenchymal–epithelial transition (MET) driver that induces miR-200 expression in prostate cancer, breast cancer, and hepatocellular carcinoma. However, little is known about the expression and function of MET in sarcomas, including OS. This study investigated the expression and clinicopathological significance of Ovol2 and its effect on MET in OS. PATIENTS AND METHODS: The Ovol2 expression in the tumor samples from patients with OS was examined using immunohistochemistry (IHC). We then upregulated the Ovol2 expression in MG-63 and SW1353 cells, detected the expression of MET-associated proteins, and observed the effects of Ovol2 on OS cell proliferation, migration, and cytoskeleton reorganization using Cell Counting Kit-8, transwell invasion, and phalloidin dyeing assays, respectively. The correlation between zinc finger E-box-binding homeobox 1 (ZEB1) and Ovol2 was assessed using the luciferase gene reporter assay in the MG-63 and SW1353 cells and IHC in the human OS tissue samples. RESULTS: The Ovol2 protein overexpression was related to the clinical grade (P=0.02) and the recurrence and metastasis (P=0.02) of OS. Results of the in vitro experiments showed that Ovol2 overexpression can suppress cell migration and invasion and can regulate the expression levels of MET-associated proteins. Ovol2 suppresses ZEB1 expression by binding to the ZEB1 promoter. Ovol2 is concomitant with a reduced IHC expression of ZEB1 in human OS tissues. CONCLUSION: Ovol2 expression is associated with MET in OS cells and suppresses ZEB1 expression and OS progression.