关键词: 14-3-3 protein Alzheimer’s disease DEGs EBV miRNA

来  源:   DOI:10.3389/fmolb.2024.1353828   PDF(Pubmed)

Abstract:
UNASSIGNED: Several studies have revealed that Epstein-Barr virus (EBV) infection raised the likelihood of developing Alzheimer\'s disease (AD) via infecting B lymphocytes. The purpose of the current investigation was to assess the possible association between EBV infection and AD.
UNASSIGNED: The microarray datasets GSE49628, GSE126379, GSE122063, and GSE132903 were utilized to extract DEGs by using the GEO2R tool of the GEO platform. The STRING tool was used to determine the interaction between the DEGs, and Cytoscape was used to visualize the results. The DEGs that were found underwent function analysis, including pathway and GO, using the DAVID 2021 and ClueGo/CluePedia. By using MNC, MCC, Degree, and Radiality of cytoHubba, we identified seven common key genes. Gene co-expression analysis was performed through the GeneMANIA web tool. Furthermore, expression analysis of key genes was performed through GTEx software, which have been identified in various human brain regions. The miRNA-gene interaction was performed through the miRNet v 2.0 tool. DsigDB on the Enrichr platform was utilized to extract therapeutic drugs connected to key genes.
UNASSIGNED: In GEO2R analysis of datasets with |log2FC|≥ 0.5 and p-value <0.05, 8386, 10,434, 7408, and 759 genes were identified. A total of 141 common DEGs were identified by combining the extracted genes of different datasets. A total of 141 nodes and 207 edges were found during the PPI analysis. The DEG GO analysis with substantial alterations disclosed that they are associated to molecular functions and biological processes, such as positive regulation of neuron death, autophagy regulation of mitochondrion, response of cell to insulin stimulus, calcium signaling regulation, organelle transport along microtubules, protein kinase activity, and phosphoserine binding. Kyoto Encyclopedia of Genes and Genomes analysis discovered the correlation between the DEGs in pathways of neurodegeneration: multiple disease, cell cycle, and cGMP-PKG signaling pathway. Finally, YWHAH, YWHAG, YWHAB, YWHAZ, MAP2K1, PPP2CA, and TUBB genes were identified that are strongly linked to EBV and AD. Three miRNAs, i.e., hsa-mir-15a-5p, hsa-let-7a-5p, and hsa-mir-7-5p, were identified to regulate most of hub genes that are associated with EBV and AD. Further top 10 significant therapeutic drugs were predicted.
UNASSIGNED: We have discovered new biomarkers and therapeutic targets for AD, as well as the possible biological mechanisms whereby infection with EBV may be involved in AD susceptibility for the first time.
摘要:
一些研究表明,EB病毒(EBV)感染通过感染B淋巴细胞增加了患阿尔茨海默病(AD)的可能性。当前研究的目的是评估EBV感染与AD之间的可能关联。
通过使用GEO平台的GEO2R工具,利用微阵列数据集GSE49628、GSE126379、GSE122063和GSE132903来提取DEG。STRING工具用于确定DEG之间的相互作用,和Cytoscape用于可视化结果。发现的DEG进行了功能分析,包括通路和GO,使用DAVID2021和ClueGo/CluePedia。通过使用MNC,MCC,学位,和cytoHubba的放射性,我们确定了七个常见的关键基因。通过GeneMANIA网络工具进行基因共表达分析。此外,通过GTEx软件对关键基因进行表达分析,已经在人脑的各个区域被发现。通过miRNetv2.0工具进行miRNA-基因相互作用。Enrichr平台上的DsigDB用于提取与关键基因相关的治疗药物。
在具有|log2FC|≥0.5和p值<0.05的数据集的GEO2R分析中,鉴定了8386、10,434、7408和759个基因。通过组合不同数据集的提取基因,总共鉴定了141个常见的DEG。在PPI分析期间共发现141个节点和207条边。具有实质性改变的DEGGO分析揭示了它们与分子功能和生物过程有关,比如神经元死亡的正向调节,线粒体的自噬调节,细胞对胰岛素刺激的反应,钙信号调节,细胞器沿着微管运输,蛋白激酶活性,和磷酸丝氨酸结合。京都基因百科全书和基因组分析发现了神经变性途径中DEGs之间的相关性:多种疾病,细胞周期,和cGMP-PKG信号通路。最后,是啊,YWHAG,YWHAB,YWHAZ,MAP2K1,PPP2CA,和TUBB基因被鉴定为与EBV和AD密切相关。三个miRNA,即,hsa-mir-15a-5p,hsa-let-7a-5p,还有hsa-mir-7-5p,被鉴定为调节大多数与EBV和AD相关的hub基因。进一步预测了前10名重要治疗药物。
我们发现了AD的新生物标志物和治疗靶点,以及EBV感染可能首次参与AD易感性的可能生物学机制。
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