Comprehensive Bioinformatics Analysis of mRNA Expression Profiles and Identification of a miRNA-mRNA Network Associated with the Pathogenesis of Low-Grade Gliomas.

Abstract

PurposeLow-grade glioma is the most common type of primary intracranial tumour, and the overall survival of patients with low-grade glioma (LGG) has shown no significant improvement over the past few decades. Therefore, it is crucial to understand the precise molecular mechanisms involved in the carcinogenesis of LGG.MethodsTo investigate the regulatory mechanisms of mRNA–miRNA networks related to LGG, in the present study, a comprehensive analysis of the genomic landscape between low-grade gliomas and normal brain tissues from the GEO and TCGA datasets was first conducted to identify differentially expressed genes (DEGs) and differentially expressed miRNAs in LGG. Following a series of analyses, including WGCNA, GO and KEGG analyses, PPI and key model analyses, and survival analysis of the DEGs with clinical phenotypes, the potential key genes were screened and identified, and the related miRNA–mRNA networks were subsequently constructed through miRWalk 3.0. Finally, the potential miRNA–mRNA networks were further validated in CGGA (Chinese Glioma Genome Atlas) datasets and clinical specimens by qRT-PCR.ResultsIn our results, six hub genes, MELK, NCAPG, KIF4A, NUSAP1, CEP55, and TOP2A, were ultimately identified. Two regulatory pathways, miR-495-3p-TOP2A and miR-1224-3p-MELK, that regulate the pathogenesis of LGG were ultimately identified. Furthermore, the expression of miR-495-3p-TOP2A and miR-1224-3p-MELK in solid tissues was validated by qRT-PCR.ConclusionOur study identified hub genes and related miRNA–mRNA regulatory pathways that contribute to the carcinogenesis of LGG, which may help us reveal the mechanisms underlying the development of LGG.