construction and analysis of a lncRNAmiRNA-mRNA network based on competitive endogenousRNA reveal prognostic biomarkers for glioblastoma multiforme

Background: Glioblastoma multiforme (GBM) is introducedas the most aggressive type of astrocytoma and one of the mostfrequent types of primary adult brain tumors. Numerous researchhas indicated that competitive endogenous RNA (ceRNA)network was associated with GBM development. However,their molecular mechanisms and functional roles in theGBM are poorly understood.Materials and Methods: We demonstrated the differentiallyexpressed lncRNA (DEL; lnc۲cancer V.۳) and mRNA(DEG; GEPIA۲) from the TCGA-GBM and miRNAs (DEM;GSE۶۵۶۲۶) from GEO. The mirDIP ۵.۲.۸.۱ and DIANALncBasev۳ were employed to predict the potential regulatoryinteractions between DELs, DEM, and DEGs. Using these data,a ceRNA network was constructed by Cytoscape. The proteinproteininteraction (PPI) network of the DEGs of CeRNA networkwas established and the top ۱۰ hub genes were uncovered.The impact of the hub genes on overall survival (OS) of GBMpatients were assessed by the GSCA. GBM related pathwayswere determined through functional enrichment analysis byEnrichr-KG. Potential drug and molecules related to GBM werepredicted by DGIdb V۴.۱.Results: In total, ۸۹۲ DEL, ۲۳۵ DEM, and ۷۲۲۶ DEGs weredemonstrated in GBM. Our ceRNA network contained ۷۵DELs, ۹۱ DEMs, and ۱۲۱۹ DEGs. The PPI network consistedof ۱۱۸۶ nodes and ۱۰۷۷۸ edges. Among the top ۱۰ hub genes(CDC۴۲, VEGFA, RHOA, MYC, CTNNB۱, JUN, NOTCH۱,STAT۳, HDAC۱, HIF۱A), CTNNB۱ and STAT۳ were associatedwith the OS. The DEGs in the PPI network were mainlyenriched in Proteoglycans in cancer, Focal adhesion, Pathwaysin cancer, MAPK signaling pathway, PI۳K-Akt signaling pathways.۱۷ and ۲۳ drugs and small molecules were interactedwith CTNNB۱ and STAT۳, respectively.Conclusion: The obtained ceRNA network, their PPI and relatedpathways may deepen our understanding to the pathogenesisof GBM. The CTNNB۱ and STAT۳ can be considered asnovel therapeutic targets and prognostic biomarkers for patientswith GBM.