Microarray data analysis of neuroblastoma: Expression of SOX2 downregulates the expression of MYCN

Abstract

Abstract. The present study aimed to identify the genes directly or indirectly correlated with the amplification of MYCN in neuroblastoma (NB). Microarray data (GSE53371) were downloaded from Gene Expression Omnibus, and included 10 NB cell lines with MYCN amplification and 10 NB cell lines with normal MYCN copy numbers. Differentially expressed genes (DEGs) were identified using the Linear Models for Microarray Data package, and a false discovery rate of <0.05 and |log 2 FC (fold change)|>1 were selected as cut-off criteria. Hierarchical clustering analysis and Gene Ontology analysis were respectively performed for the DEGs using the Pheatmap package in R language and The Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction network (PPI) was constructed for the DEGs using the Search Tool for the Retrieval of Interacting Genes database. Pathway analysis was performed for the DEGs in the PPI network using the WEB-based GEne SeT AnaLysis Toolkit. The correlation between MYCN and the key gene associated with MYCN was determined using Pearson's correlation coefficient. In total, 137 downregulated and 35 upregulated DEGs were identified. Functional enrichment analysis indicated that KCNMB4 was involved in the regulation of action potential in neuron term, and the FOS, GLI3 and GLI1 genes were involved in the extracellular matrix-receptor interaction pathway. The PPI network and correlation analysis revealed that the expression of SOX2 was directly correlated with the expression of MYCN, and the correlation coefficient of SOX2 and MYCN was -0.83. Therefore, SOX2, KCNMB4, FOS, GLI3 and GLI1 may be involved in the pathogenesis of NB, with the expression of SOX2 downregulating the expression of MYCN.

In vitro Charakterisierung von Cisplatin-resistenten Neuroblastom-Sublinien

“…119 Beim Mensch ist das Gen SOX-2 auf Chromosom 3q26.33 lokalisiert. 120 Bei der Maus wird die Transkription unter anderem durch mehrere Enhancer und einen basalen Promoter reguliert. 121 Von…”

“…Uneinigkeit herrscht im Bezug auf den Zusammenhang zwischen SOX-2 und MYCN. Eine Gruppe fand eine negative Korrelation zwischen SOX-2 und MYCN sowie Regulation von SOX-2 durch die Signalwege von GLI1 und FOX 120. Im Gegensatz dazu fand eine Gruppe, dass Herunterregulation von MYCN (durch ATRA) zur Erniedrigung von SOX-2 , Oct-4, Nanog und NCYM führt 93.…”