Preliminary Study Of IDH1 Mutations Promote Glioma Malignant Behavior Via EMT

Glioma,as one of the most common malignant tumors of central nervous system,is still not to be conquered by human,and as a disease to cause serious damage to health and quality of human life.Based on its histopathological characteristics,the World Health Organization(WHO)have divided glioma into grade ?-? in central nervous system.And with the progression of further research in glioma,the traditional characteristic of histopathological classification can not explain so many clinical phenomena,also with the continuous progress of the molecular genetic fronts show the deficiency of the clinical treatment and prognosis guidance,in molecular genetic studies on glioma,Isocitrate Dehydrogenase Gene(IDH)mutant showed great clinical guiding significance,is also worthy of further research.IDH mutation is leading to study and put forward in 2009 by Dang,L.And the experiment proved that IDH mutation can lead to accumulation of cancer metabolite 2-hydroxyglutamte(2-HG),and a high level of 2-HG can induce the occurrence and malignant progress of glioma.Most researchers study of IDH mutation concentrated in the 293T and glioblastoma cells,such as cell lines,while clinical data suggest that IDH mutation occured in the lower level glioma(>80%),while the cell lines are different from the clinical patients.This applying of primary low grade glioma cell research is quite meaningful.IDH genes can express Isocitrate Dehydrogenase,under the physiological level according to the different parts of the distribution can be divided into three subtypes,IDH1,IDH2 and IDH3.IDH1 is located in the cytoplasm,while IDH2 and IDH3 are located in the mitochondria,its function,so the IDH1 which can reflect the features of the IDH and more representative.2-HG,as the metabolites generated by IDH mutation,promote tumor progression has become key research targets because of its close relationship with IDH mutation.Previous studies have found that cell genome and histone methylation,and cell differentiation are restrained after IDH1 mutations,and studies have shown that IDH1 mutations as well as the exogenous 2-HG can induce changes in the epithelial cells,which are not verified in glioma,especially lower grade glioma.And the effects of IDH1 mutations tumor progression can't explain the favour prognosis of IDH mutation glioma.The purpose of this study is to investigate the mechanism of isocitrate dehydrogenase 1(IDH1)and its metabolites 2-hydroxyglutarate(2-HG)on proliferation,migration.Previous study have shown in normal breast epithelium cells and colorectal cancer cells.IDH mutation can affect the epithelial cells in the morphology and function,and mechanism of it have not proved in glioma yet.Our research practicing the generation of cell culture and cell line as experiment object,cell proliferation experiment(CCK-8)to detect cell proliferation,migration ability to scratch test cells,applying polymerase chain reaction(PCR)to test the epithelial cells of the mRNA expression of related genes.Experiments show that IDH mutation glioma cells and exogenous 2-HG treated glioblastoma cells form interstitial change will happen,with increasing 2-HG concentration being more obvious;IDH mutation promote the glioma cell proliferation and migration ability,epithelial markers E-Cadherin,being the expression of sticky protein,raised expression of mesenchymal cells markers Vimentin and beta chain protein(beta-catenin).So we can conclude that IDH mutation or its metabolite 2-HG can promote IDH wild-type glioblastoma in proliferation and migration via EMT.