Bioinformatics analysis of microarray data to reveal the pathogenesis of diffuse intrinsic pontine glioma

Abstract

BackgroundDiffuse intrinsic pontine glioma (DIPG) is the main cause of pediatric brain tumor death. This study was designed to identify key genes associated with DIPG.MethodsThe gene expression profile GSE50021, which consisted of 35 pediatric DIPG samples and 10 normal brain samples, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified by limma package. Functional and pathway enrichment analyses were performed by the DAVID tool. Protein–protein interaction (PPI) network, and transcription factor (TF)–microRNA (miRNA)–target gene network were constructed using Cytoscape. Moreover, the expression levels of several genes were validated in human glioma cell line U251 and normal glia HEB cells through real-time polymerase chain reaction (PCR).ResultsA total of 378 DEGs were screened (74 up-regulated and 304 down-regulated genes). In the PPI network, GRM1, HTR2A, GRM7 and GRM2 had higher degrees. Besides, GRM1 and HTR2A were significantly enriched in the neuroactive ligand–receptor interaction pathway, and calcium signaling pathway. In addition, TFAP2C was a significant down-regulated functional gene and hsa-miR-26b-5p had a higher degree in the TF-miRNA-target gene network. PCR analysis revealed that GRM7 and HTR2A were significantly downregulated while TFAP2C was upregulated in U251 cells compared with that in HEB cells (p < 0.001). GRM2 was not detected in cells.ConclusionsGRM1 and HTR2A might function in DIPG through the neuroactive ligand–receptor interaction pathway and the calcium signaling pathway. Furthermore, the TFAP2C and hsa-miR-26b-5p might play important roles in the development and progression mechanisms of DIPG.

In silico identification of the prognostic biomarkers and therapeutic targets associated with cancer stem cell characteristics of glioma

“…Generally, the tumorigenesis and progression of glioma is significantly with its microenvironment. The microenvironment cells interact with glioma cells with neuroactive ligand–receptor interaction [ 28 , 29 ].…”

Identification of Dysregulated Pathways and key genes in Human Retinal Angiogenesis using Microarray Metadata

“…Among the several DEGs involved in neuroactive ligand receptor interaction pathway, though our angiome-network showed no angiogenic-associated genes, ADRA1B 27 , CHRM2 28 , DRD4 29 , GALR3 30 , GLP2R 31 , GRIN2C 32 , GRIN2D 33 , HTR5A 34 , P2RY2 35 , UTS2R 36 DEGs have been reported to be involved in angiogenesis. The neuroactive ligand receptor interaction pathway has been reported to be the most significant pathway for cancers and angiogenesis and is also closely connected with the poor prognosis of cancer 37–41 .…”

Identification of microRNAs Targeting the Transporter Associated with Antigen Processing TAP1 in Melanoma

“…Gene Ontology (GO) analysis was performed using the respective database ( ) enrichment analysis. Predicted target gene candidates of miRs identified in this study [ 66 ] were categorized regarding their function into the biological process (BP), molecular function (MF), and cellular component (CC) [ 67 ]. It provides all GO terms significantly enriched in the predicted target gene candidates of the enriched known as well as novel identified miRs compared to the reference gene background (in this study the MS2 control) as well as the genes corresponding to certain biological functions.…”

“…It provides all GO terms significantly enriched in the predicted target gene candidates of the enriched known as well as novel identified miRs compared to the reference gene background (in this study the MS2 control) as well as the genes corresponding to certain biological functions. The corrected p-value (q-value) of <0.05 and the gene count of ≥2 was chosen as a significant threshold [67].…”