Abstract
BackgroundGlioma accounts for a large proportion of cancer, and an effective treatment for this disease is still lacking because of the absence of specific driver molecules. Current challenges in the treatment of glioma are the accurate and timely diagnosis of brain glioma and targeted treatment plans. To investigate the diagnostic biomarkers and prospective role of miRNAs in the tumorigenesis and progression of glioma, we analyzed the expression of miRNAs and key genes in glioma based on The Cancer Genome Atlas database.MethodsOf the 701 cases that were downloaded, five were normal and 696 were glioma. Then, 1626 differentially expressed genes were identified, and 173 aberrantly expressed miRNAs were calculated by edgeR. GO and KEGG pathway enrichment analyses were performed using Cytoscape software. A coexpression network was built by weighted correlation network analysis (WGCNA). A cell scratch test and transwell, cell apoptosis and cell cycle assays were performed to validate the function of hsa-let-7b-5p.ResultsBased on crosstalk genes in the KEGG, PPI network, and WGCNA analyses, PLK1, CCNA2, cyclin B2 (CCNB2), and AURKA were screened as candidate diagnostic marker genes. The survival analysis revealed that high mRNA expression of PLK1, CCNA2, and AURKA was significantly associated with poor overall survival. Furthermore, hsa-let-7b-5p was identified as a core miRNA in the regulation of candidate genes involved in glioma development. We confirmed that hsa-let-7b-5p could inhibit the migration, invasion, and cell cycle of glioma cells.ConclusionsThis study provides four potential biomarkers for the diagnosis of glioma, offers a potential explanation of its pathogenesis, and proposes hsa-let-7b-5p as a therapeutic target.
Highlights
Glioma accounts for a large proportion of cancer, and an effective treatment for this disease is still lacking because of the absence of specific driver molecules
The results showed that hsa-let-7b-5p could regulate target genes, including cell cycle protein A2 (CCNA2), cyclin B2 (CCNB2), polo-like kinase 1 (PLK1), and AURKA, and further affect the progress of glioma
Identification of differentially expressed genes (DEGs) based on The Cancer Genome Atlas (TCGA) data in glioma A total of 17,746 genes from 5 normal samples and 696 glioma samples were obtained
Summary
Glioma accounts for a large proportion of cancer, and an effective treatment for this disease is still lacking because of the absence of specific driver molecules. Previous studies on glioma have revealed many molecular markers, such as IDH, 1p19q, MGMT, sarcomarcoma proto oncogene B, telomerase reverse transcriptase tert, and epidermal growth factor receptor [5,6,7]. Among these molecular markers, IDH1, 1p19q, and MGMT methylation are closely associated with the prognosis and. Xi et al J Transl Med (2019) 17:129 chemotherapy sensitivity of glioma patients [8,9,10,11] These markers have limited sensitivity and accuracy [12]. Specific and novel early diagnostic markers are necessary to understand the pathogenesis of glioma
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