The Clinical Significance Of Epithelial-mesenchymal Transition (EMT) In Brain Gliomas And The Study Of Related Regulatory MiRNAs

Part One: The clinical significance of the epithelialmesenchymal transition(EMT)in glioma[Objective] Epithelial-to-mesenchymal transition(EMT)is a complex cellular process reflecting a high level of phenotypic plasticity.Epithelial tumors achieve this progressive state via EMT.The purpose of this study was to analyze the clinical significance of EMT in glioma based on the high throughout RNA-sequencing data.[Methods] In this study,a total of 325 glioma samples with Whole transcriptome sequencing data from the Chinese Glioma Genome Atlas(CGGA)were analyzed(all samples completed long-term follow-up of clinical information).The correlation between EMT biological process and some factors(such as: tumor grades,clinical outcome,molecular subtypes and IDH mutation status)was further analyzed.Finally,the clinical significance of EMT biological processes was verified through public databases such as GSE16011,Rembrandt and TCGA.[Results] In Chinese glioma patients,EMT biological process was positively correlated with malignant grades,highly activated in mesenchymal glioma,and significantly correlated with IDH1 mutation.Survival analysis found that EMT biological process was significantly correlated with the prognosis of glioma patients,and EMT process was an important predictor of poor prognosis of patients with glioma.Further analysis verified the clinical significance of EMT biological process in the GSE16011,Rembrandt,and TCGA databases.[Conclusion] Overall,we systematically elucidate the significance of EMT biological process in the malignant progression of glioma and its correlation with clinical prognosis based on the genomics database of glioma.Part Two: Genome-wide identification of epithelial-mesenchymal transition-associated micro RNAs reveals novel targets for glioblastoma therapy[Objective] Micro RNAs(mi RNA)regulate a number of cellular processes.Recent studies have indicated that these molecules function in the epithelial-mesenchymal transition(EMT).However,the crucial systematic role of EMT and mi RNAs together in glioblastoma(GBM)remains poorly understood.[Methods] A total of 491 TCGA GBM samples were examined in the present study.Matlab software was used to calculate the Pearson's correlation to determine the association between the mi RNAs and the EMT_up gene set enrichment score.[Results] Integrated analysis of mi RNAs and m RNA profiling in 491 GBM samples revealed an EMT biological process associated with an mi RNA profile(19 positively and 18 negatively correlated mi RNAs).Among these mi RNAs,mi R-95 and mi R-223 indicated a high level of functional validation,reflecting their positive correlation with EMT.Additionally,the upregulation of mi R-95,which was negatively correlated with EMT,inhibited cellular invasion in glioma U251 and LN229 cells and decreased the expression of the mesenchymal marker N-catenin,whereas an mi RNA positively correlated with EMT,mi R-223,exhibited the opposite effect.[Conclusion] Therefore,the results of the present study could further enhance the current understanding of the functions of mi RNAs in GBM,indicating that the EMT-specific mi RNA signature may represent a novel target for GBM therapy.