WITHDRAWN: Bioinformatic analysis of the roles of CDK2 in neuroblastoma

Abstract

Abstract Objective This study aimed to elucidate the potential mechanism of cyclin-dependent kinase 2 (CDK2) in neuroblastoma progression and to identify the key genes associated with neuroblastoma with CDK2 silencing. Materials and Methods GSE16480 microarray data were downloaded from the gene expression omnibus (GEO) database. This dataset contains 15 samples: neuroblastoma IMR32 cells were transfected with CDK2 shRNA for 0, 8, 24, 48 and 72 h, respectively (n = 3 per group; total = 15). Significant clusters associated with differentially expressed genes (DEGs) were identified using the fuzzy C-Means algorithm in the Mfuzz package. Gene ontology (GO) and pathway enrichment analyses of DEGs in each cluster were performed, and protein–protein interaction (PPI) networks were constructed. Functional annotation of DEGs in clusters was performed to detect transcription factors (TFs) and tumour-associated genes (TAGs). Results Four clusters of 337 up-regulated DEGs, 649 down-regulated DEGs, 387 down-regulated DEGs and 310 up-regulated DEGs were identified. The hub nodes of the PPI network constructed by DEGs in Clusters 1–4 included MDM2 oncogene, E3 ubiquitin protein ligase ( MDM2 ), cyclin-dependent kinase 1 ( CDK1 ), proteasome (prosome, macropain) 26S subunit, non-ATPase, 14 ( PSMD14 ) and translocator protein (18 kDa) ( TSPO ). The significantly-enriched genes had functions related to p53 signalling (Cluster 1), the cell cycle (Cluster 2), proteasomes (Cluster 3) and systemic lupus erythematosus (Cluster 4). Conclusion MDM2 , CDK1 , PSMD14 and TSPO may be key target genes of CDK2. CDK2 may play important roles in neuroblastoma progression by regulating the expression of these genes and their related pathways.