Regulation of human glioma cell apoptosis and invasion by miR-152-3p through targeting DNMT1 and regulating NF2: MiR-152-3p regulate glioma cell apoptosis and invasion

Background: mirnas are involved in aberrant dna methylation through regulation of dna methyltransferases (dnmts) in the pathogenesis and progression of glioblastomas (gbm). mir-152-3p was down-expressed in human malignancies,and served as a tumor suppressor. neurofibromatosis type 2 (nf2) was significantly decreased in gbm tissues with a high level of methylation. however,the link between mir-152-3p,dnmt1 and methylation of nf2 in gbm is not clearly established. this study was conducted to detect the mechanism between mir-152-3p,dnmt1 and nf2 in gbm. methods: the levels of dnmt1 and nf2 expression were studied by qrt-pcr,western blot,immunofluorescence,and immumohistochemical staining. methylation in the promoter region of nf2 was detected by methylation-specific pcr and bisulfate genomic sequencing pcr. cell proliferation was examined by cell-counting kit-8 and 5-ethynyl-2′-deoxyuridine assay,and cell invasion was evaluated by transwell assay. flow cytomery and hoechst staining were used to analyze cell apoptosis. a dual luciferase system was used to confirm the relationship between mir-152-3p and dnmt1. results: methylation of nf2 and dnmt1 was markedly increased,and mir-152-3p was downregulated in gbm tissues and glioma cells. both knockdown of dnmt1 and overexpression mir-152-3p showed that demethylation activated the expression of nf2. furthermore,mir-152-3p directly targeted dnmt1. both mir-152-3p overexpression and dnmt1 knockdown significantly induced cell apoptosis and inhibited invasive activity. this was also observed after nf2 overexpression. conclusions: these results indicated that mir-152-3p can inhibit glioma cell proliferation and invasion activities by decreasing dnmt1. the restoration of mir-152-3p may have therapeutic application in the treatment of gbm. © 2017 the author(s).