TGF-β-mediated repression of MST1 by DNMT1 promotes glioma malignancy

Human gliomas are related to high rates of morbidity and mortality. TGF-beta promotes the growth of glioma cells, and correlate with the degree of malignancy of human gliomas. However, the molecular mechanisms involved in the malignant function of TGF-beta are not fully elucidated. Here, we showed that TGF-beta induced the downregulation of MST1 expression in U87 and U251 glioma cells. Treatment of glioma cells with the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-AzadC) prevented the loss of MST1 expression. Addition of 5-AzadC also reduced the TGF-beta-stimulated proliferation, migration and invasiveness of glioma cells. Furthermore, Knockdown of DNMT1 upregulated MST1 expression in gliomas cells. In addition, the inhibition of DNMT1 blocked TGF-beta-induced proliferation, migration and invasiveness in glioma cells. These results suggest that TGF-beta promotes glioma malignancy through DNMT1-mediated loss of MST1 expression. (C) 2017 Published by Elsevier Masson SAS.