Abstract
Glioma is an extremely aggressive malignant neoplasm of the central nervous system. MicroRNA (miRNA) are known to bind to specific target mRNA to regulate post-transcriptional gene expression and are, therefore, currently regarded as promising biomarkers for glioma diagnosis and prognosis. The aim of the present study was to examine the pathogenesis and potential molecular markers of glioma by comparing the differential expression of miRNA and mRNA between glioma tissue and peritumor brain tissue. We explored the impact of screened core miRNA and mRNA on cell proliferation, invasion, and migration of glioma. An miRNA expression profile dataset (GSE90603) and a transcriptome profile dataset (GSE90598) were downloaded from combined miRNA-mRNA microarray chips in the Gene Expression Omnibus (GEO) database. Overall, 59 differentially expressed miRNAs (DEMs) and 419 differentially expressed genes (DEGs) were identified using the R limma software package. FunRich software was used to predict DEM target genes and miRNA-gene pairs, and Perl software was used to find overlapping genes between DEGs and DEM target genes. There were 129 overlapping genes regulated by nine miRNAs between target genes of the DEMs and DEGs. The Chinese Glioma Genome Atlas(CGGA) was analyzed in order to identify miRNAs with diagnostic and prognostic significance. MiR-139-5p, miR-137, and miR-338-3p were validated to be significantly linked to prognosis in glioma patients. Finally, we validated that miR-139-5p affected glioma malignant biological behavior via targeting gamma-aminobutyric acid A receptor alpha 1(GABRA1) through rescue experiments. Low miR-139-5p expression was correlated with survival probability and World Health Organization (WHO) grade. MiR-139-5p overexpression inhibited cell proliferation, migration, and invasion of glioma in vitro. GABRA1 was identified as a functional downstream target of miR-139-5p. Decreased GABRA1 expression was related to similar biological roles as miR-139-5p overexpression while upregulation of GABRA1 effectively reversed the inhibition effects of miR-139-5p. These results demonstrate a novel axis for miR-139-5p/GABRA1 in glioma progression and provide potential prognostic predictors and therapeutic target for glioma patients.
Highlights
Glioma is the most prevalent primary malignant neoplasm in the central nervous system, with high recurrence and mortality rates
We identified that miR-139-5p and GABRA1 served as inverse agents in the regulation of malignant phenotypes of glioma cells, we doubted whether the function of miR-139-5p on glioma cells was mediated through its inhibitory impression on GABRA1 expression
Identification of differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) in GBM Using the GSE90603 dataset, 59 DEMs were identified in the GBM samples compared with the peritumoral tissues, of which 37 were upregulated and 22 were downregulated (Additional file 1)
Summary
Glioma is the most prevalent primary malignant neoplasm in the central nervous system, with high recurrence and mortality rates. The higher the grade of the glioma, the worse the prognosis of the patient. Glioblastoma multiforme(GBM), represents the most aggressive glioma subtype, with a five-year survival rate of less than 3% and average survival of less than 12 months [2]. The 3-year survival rate remains at a low level, Wang et al J Transl Med (2021) 19:213 especially for GBM patients, with the 3-year survival rate only slightly increasing from 2.00%–5.00% to 7.31% [4]. Researchers have turned their attention to study the potential molecular mechanisms of GBM, and to find novel prognostic biomarkers for the early diagnosis and monitoring of tumorigenesis and for evaluating prognosis
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