Department of Infections, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Department of Neurosurgery, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Mol Med Rep. 2018 Mar;17(3):3951-3959. doi: 10.3892/mmr.2017.8368. Epub 2017 Dec 29.
The present study aimed to elucidate the potential mechanism of cyclin-dependent kinase 2 (CDK2) in neuroblastoma progression and to identify the candidate genes associated with neuroblastoma with CDK2 silencing. The microarray data of GSE16480 were obtained from the gene expression omnibus database. This dataset contained 15 samples: Neuroblastoma cell line IMR32 transfected with CDK2 shRNA at 0, 8, 24, 48 and 72 h (n=3 per group; total=15). Significant clusters associated with differentially expressed genes (DEGs) were identified using fuzzy C‑Means algorithm in the Mfuzz package. Gene ontology and pathway enrichment analysis of DEGs in each cluster were performed, and a protein‑protein interaction (PPI) network was constructed. Additionally, functional annotation of DEGs in clusters was performed for the detection of transcription factors and tumor‑associated genes. A total of 4 clusters with significant change tendency and 1,683 DEGs were identified. The hub nodes of the PPI network constructed by DEGs in Cluster 1, Cluster 2, Cluster 3 and Cluster 4 were 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) respectively. These genes were significantly enriched in the p53 signaling pathway, cell cycle, proteasome and systemic lupus erythematosus pathways. MDM2, CDK1, PSMD14 and TSPO may be key target genes of CDK2. CDK2 may have key functions in neuroblastoma progression by regulating the expression of these genes.
本研究旨在阐明细胞周期蛋白依赖性激酶 2（CDK2）在神经母细胞瘤进展中的潜在机制，并确定与 CDK2 沉默相关的神经母细胞瘤候选基因。从基因表达综合数据库中获得了 GSE16480 的微阵列数据。该数据集包含 15 个样本：CDK2 shRNA 转染的神经母细胞瘤细胞系 IMR32 在 0、8、24、48 和 72 h（每组 3 个样本；共 15 个样本）。使用 Mfuzz 包中的模糊 C-Means 算法识别与差异表达基因（DEG）相关的显著聚类。对每个聚类中的 DEG 进行基因本体论和途径富集分析，并构建蛋白质-蛋白质相互作用（PPI）网络。此外，对聚类中 DEG 的功能注释进行了转录因子和肿瘤相关基因的检测。共鉴定出 4 个具有显著变化趋势的聚类和 1683 个 DEG。由 Cluster 1、Cluster 2、Cluster 3 和 Cluster 4 中的 DEG 构建的 PPI 网络的核心节点分别为 MDM2 癌基因、E3 泛素蛋白连接酶（MDM2）、细胞周期蛋白依赖性激酶 1（CDK1）、蛋白酶体（蛋白酶体、巨蛋白酶）26S 亚基、非-ATP 酶、14（PSMD14）和转位蛋白（18 kDa）（TSPO）。这些基因在 p53 信号通路、细胞周期、蛋白酶体和系统性红斑狼疮途径中显著富集。MDM2、CDK1、PSMD14 和 TSPO 可能是 CDK2 的关键靶基因。CDK2 可能通过调节这些基因的表达在神经母细胞瘤进展中发挥关键作用。
