Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Mol Med Rep. 2018 Mar;17(3):3775-3782. doi: 10.3892/mmr.2017.8305. Epub 2017 Dec 18.
The present study aimed to examine potential crucial genes associated with Parkinson's disease (PD) in addition to the interactions and regulators of these genes. The chip data (GSE7621) were obtained from the Gene Expression Omnibus and standardized using the robust multi‑array average in the Affy package of R software. The differentially expressed genes (DEGs) were then screened using the Samr package with a false discovery rate (FDR) <0.05 and |log2 fold change (FC)|>1. Crucial PD‑associated genes were predicted using the Genetic Association Database in the Database for Annotation, Visualization and Integrated Discovery and sequence alignment. Furthermore, transcription factors (TFs) of the crucial PD‑associated genes were predicted, and protein‑protein interactions (PPIs) between the crucial PD‑associated genes were analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins. Additionally, another dataset of PD was used to validate the expression of crucial PD‑associated genes. A total of 670 DEGs (398 upregulated and 272 downregulated genes) were identified in the PD samples. Of these, 10 DEGs enriched in pathways associated with the nervous system were predicted to be crucial in PD, including C‑X‑C chemokine receptor type 4 (CXCR4), deleted in colorectal cancer (DCC) and NCL adaptor protein 2 (NCK2). All 10 genes were associated with neuron development and differentiation. They were simultaneously modulated by multiple TFs, including GATA, E2F and E4 promoter‑binding protein 4. The PPI networks showed that DCC and CXCR4 were hub proteins. The DCC‑netrin 1‑roundabout guidance receptor 2‑slit guidance ligand 1 interaction pathway, and several genes, including TOX high mobility group box family member 4, kinase insert domain receptor and zymogen granule protein 16B, which interacted with CXCR4, were novel findings. Additionally, CXCR4 and NCK2 were upregulated in another dataset (GSE8397) of PD. These genes, interactions of proteins and TFs may be important in the progression of PD.
本研究旨在探讨与帕金森病（PD）相关的潜在关键基因，以及这些基因的相互作用和调控因子。芯片数据（GSE7621）从基因表达综合数据库中获得，并使用 R 软件的 Affy 包中的稳健多阵列平均进行标准化。然后使用 Samr 包筛选差异表达基因（DEGs），假发现率（FDR）<0.05，|log2 倍数变化（FC）|>1。使用 Genetic Association Database 数据库预测与 PD 相关的关键基因，并进行序列比对。此外，还预测了与关键 PD 相关基因的转录因子（TFs），并使用 Search Tool for the Retrieval of Interacting Genes/Proteins 分析了关键 PD 相关基因之间的蛋白质-蛋白质相互作用（PPIs）。此外，还使用另一个 PD 数据集验证了关键 PD 相关基因的表达。在 PD 样本中鉴定出 670 个 DEGs（398 个上调和 272 个下调基因）。其中，有 10 个 DEGs 富集在与神经系统相关的途径中，被预测为 PD 中的关键基因，包括 C-X-C 趋化因子受体 4（CXCR4）、结直肠癌缺失基因（DCC）和 NCL 衔接蛋白 2（NCK2）。这 10 个基因均与神经元发育和分化有关。它们同时受到多个 TF 的调节，包括 GATA、E2F 和 E4 启动子结合蛋白 4。PPI 网络显示 DCC 和 CXCR4 是枢纽蛋白。DCC-神经导向因子 1-绕路导向受体 2-缝隙导向配体 1 相互作用途径，以及与 CXCR4 相互作用的几个基因，包括 TOX 高迁移率族框家族成员 4、激酶插入结构域受体和酶原颗粒蛋白 16B，是新发现的。此外，CXCR4 和 NCK2 在另一个 PD 数据集（GSE8397）中上调。这些基因、蛋白质相互作用和 TF 可能在 PD 的进展中很重要。
