Novel lncRNA -miRNA -mRNA competing endogenous RNA regulatory networks in glioma

Gliomas the most frequent type among primary brain tumors are highly heterogeneous. Understanding molecular mechanisms of glioma is crucial for developing effective therapies. Several altered signaling pathways and cross-linked relationships of ncRNAs and coding RNAs remain to be investigated. Identifying unknown interconnections between these genes may provide valuable clues for developing strategies for cancer therapy. The regulatory mechanisms of the ceRNA network in the pathogenesis of Gliomas remain to be investigated. In this study, we aimed to identify potential regulatory networks involved in glioma tumorigenesis, based on the ceRNA hypothesis. We obtained Four datasets (SRP۴۳۴۱۲۳, SRP۲۳۳۲۲۱, SRP۳۲۸۸۱۴, SRP۱۱۴۵۵۶) Which contain mRNA and lncRNA expression RNA-seq from ۳۲ glioma tissues and ۳۲ normal ones. Also, ۲ and ۱۲ samples contain miRNA-seq of glioma and ۱۲ normal tissues, respectively. Following a series of analyses such as Survival and co-expression analysis, GO and KEGG enrichment analysis, using online tools including Targetscan, miRwalk, and mirDB the interactions between lncRNA, miRNA, and targeted mRNA were predicted and visualized using Cytoscape software. We constructed a regulatory network associated with glioma tumorigenesis we acquired five axes, 'CRNDE/has-mir-۲۲۳/STAB۱', 'CRNDE۱/has-mir-۱۵۰/TOP۲', 'NEAT۱/has-mir-۱۵۰/TOP۲', 'GRM۳-AS۱/has-mir-۱۲۸/TOP۲' and 'GRM۳-AS۱/has-mir-۱۲۸/STAB۱' which were found to be related with the prognosis of glioma and present as potential ceRNA regulatory networks in glioma patients. Our results provided a potential regulatory network underlying glioma genesis and displayed that CRNDE can competitively bind to miR-۲۲۳, and miR-۱۵۰ also NEAT۱ can competitively bind to miR-۱۵۰ and miR-۱۲۸. GRM۳-AS۱ acts as a ceRNA and binds to miR-۱۲۸. Therefore, based on Functional Enrichment Analysis, modulating STAB۱ and TOP۲ expression levels in glioma, affects systemic lupus erythematosus (SLA), alcoholism, and Neutrophil extracellular trap pathways in glioma.

کلیدواژه ها:

ceRNA ، glioma ، lncRNA ، miRNA ، mRNA interactions ، prognosis