In Silico Analysis of miRNA-mediated ceRNAs as Potential Molecular Biomarkers in Glioblastoma

Abstract

Objectives: Glioblastoma multiforme (GBM) is defined as the most frequent and lethal form of the primary brain tumors in the central nervous system (CNS) in adults. Recent studies have focused on the identification of the new targets for the diagnosis and treatment of GBM and resulted in great interest for miRNAs due to their regulatory effects in cancer pathogenesis. Thus, we aimed to characterize novel molecular biomarkers for GBM by computational analysis.Methods: 118 miRNAs that are clinically related with glioblastoma and proven by experimentally were exported through miRTarBase database. 1016 genes projected by these 118 miRNAs were determined via ComiR database. Subsequently, the genes with transcribed ultraconserved regions (T-UCRs) in their exonic regions were designated and the genes which have potential competing endogenous RNA (ceRNA) activities were extracted. Genes with remarkable expression profile differences between glioblastoma and normal brain tissues among ceRNAs that are associated with glioblastoma involving T-UCR were identified. Results:The statistical analysis of the correlation between PBX3 and NRXN3 genes and glioblastoma was carried out by Spearman correlation test. PBX3 and NRXN3 expression was significantly higher and lower in glioblastoma than in normal brain tissues, respectively. On the other hand, the other genes did not have any remarkable differential expression pattern. Conclusion:Based on the findings of the current study, it is determined that NRXN3 acts as a tumor suppressor gene and NRXN3 gene is downregulated in GBM. PBX3 gene functions as an oncogene and is upregulated in GBM.

Transcriptome-wide analysis of circRNA and RBP profiles and their molecular and clinical relevance for GBM

“…We found further that both circCOL4A1 and circCOL1A2 are highly expressed in this subtype. Moreover, circCOL1A2 was previously described as upregulated in gastric cancer enhancing the migration and invasion properties [82] and also promoting angiogenesis in diabetic retinopathy [83,84], which can make circCOL1A2 a relevant marker of mesenchymal GBM subtype. For the first time, we managed to distinguish new GBM groups based on RBP expression patterns, independent of known molecular subtypes.…”