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.
Highlights
Diffuse intrinsic pontine glioma (DIPG) is the main cause of pediatric brain tumor death
Microarray data The gene expression profile GSE50021 was downloaded from the Gene Expression Omnibus database [12], which was based on the platform of GPL13938 Illumina HumanHT-12 WGDASL V4.0 expression beadchip
The up-regulated genes were significantly enriched in the modification-dependent macromolecule catabolic process (BP, p = 0.044), nucleotide binding (MF, p = 0.007), cytosolic part (CC, p = 0.044), and antigen processing and presentation (Fig. 2a)
Summary
Diffuse intrinsic pontine glioma (DIPG) is the main cause of pediatric brain tumor death. This study was designed to identify key genes associated with DIPG. Diffuse intrinsic pontine glioma (DIPG) is the most common brain tumor in childhood [1]. DIPG can be treated by radiotherapy and chemotherapy, the average survival time has remained only 9 months and 5-year survival time is less than 1% [3]. In the past few years, DIPG cell cultures and orthotopic xenograft models have been established [6, 7]. Previous study showed that grade of gliomas in human brain was related to the R-Ras expression and phosphorylation, indicating the EphB2/R-Ras signaling pathway as a potential target associated with cell adsorption, growth and invasion [8]. Holland et al [9] found that activation of Ras and Akt in neural progenitor cells can induce
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