Table_3_Meta-Analysis of Gene Expression and Identification of Biological Regulatory Mechanisms in Alzheimer's Disease.xls

Alzheimer's disease (AD), also known as senile dementia, is a progressive neurodegenerative disease. The etiology and pathogenesis of AD have not yet been elucidated. We examined common differentially expressed genes (DEGs) from different AD tissue microarray datasets by meta-analysis and screened the AD-associated genes from the common DEGs using GCBI. Then we studied the gene expression network using the STRING database and identified the hub genes using Cytoscape. Furthermore, we analyzed the microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and single nucleotide polymorphisms (SNPs) associated with the AD-associated genes, and then identified feed-forward loops. Finally, we performed SNP analysis of the AD-associated genes. Our results identified 207 common DEGs, of which 57 have previously been reported to be associated with AD. The common DEG expression network identified eight hub genes, all of which were previously known to be associated with AD. Further study of the regulatory miRNAs associated with the AD-associated genes and other genes specific to neurodegenerative diseases revealed 65 AD-associated miRNAs. Analysis of the miRNA associated transcription factor-miRNA-gene-gene associated TF (mTF-miRNA-gene-gTF) network around the AD-associated genes revealed 131 feed-forward loops (FFLs). Among them, one important FFL was found between the gene SERPINA3, hsa-miR-27a, and the transcription factor MYC. Furthermore, SNP analysis of the AD-associated genes identified 173 SNPs, and also found a role in AD for miRNAs specific to other neurodegenerative diseases, including hsa-miR-34c, hsa-miR-212, hsa-miR-34a, and hsa-miR-7. The regulatory network constructed in this study describes the mechanism of cell regulation in AD, in which miRNAs and lncRNAs can be considered AD regulatory factors.

阿尔茨海默病（Alzheimer's disease, AD）又称老年痴呆症，是一种进行性神经退行性疾病。目前其病因及发病机制尚未阐明。本研究通过荟萃分析整合不同AD组织芯片数据集的公共差异表达基因（differentially expressed genes, DEGs），并借助GCBI平台从上述公共DEGs中筛选AD相关基因；随后利用STRING数据库构建基因表达网络，并通过Cytoscape软件鉴定核心基因。此外，本研究分析了与AD相关基因存在关联的微小RNA（microRNAs, miRNAs）、长链非编码RNA（long non-coding RNAs, lncRNAs）及单核苷酸多态性（single nucleotide polymorphisms, SNPs），并鉴定出前馈环路（feed-forward loops, FFLs）。最后，本研究对AD相关基因开展了SNP分析。研究结果显示，本次共鉴定出207个公共DEGs，其中57个此前已有文献报道与AD相关。通过公共DEG表达网络共筛选得到8个核心基因，所有核心基因均已被证实与AD存在关联。进一步针对AD相关基因及其他神经退行性疾病特异性基因的调控性miRNA进行分析，共鉴定出65个AD相关miRNAs。围绕AD相关基因构建的转录因子-微小RNA-基因-基因关联转录因子（mTF-miRNA-gene-gTF）调控网络分析，共发现131个前馈环路（FFLs），其中SERPINA3基因、hsa-miR-27a与转录因子MYC之间存在一条关键前馈环路。此外，对AD相关基因的SNP分析共鉴定出173个SNPs，并发现包括hsa-miR-34c、hsa-miR-212、hsa-miR-34a及hsa-miR-7在内的其他神经退行性疾病特异性miRNA在AD中发挥调控作用。本研究构建的调控网络阐明了AD的细胞调控机制，其中miRNAs与lncRNAs可被视为AD的潜在调控因子。