Investigating gene expression datasets of hippocampus tissue to discover Alzheimer's disease-associated molecular markers.

IF 3.4 3区医学 Q2 NEUROSCIENCES Journal of Alzheimer's Disease Pub Date : 2024-11-27 DOI:10.1177/13872877241297335

Sneh Prabha, Mohd Sajad, Farah Anjum, Md Imtaiyaz Hassan, Anas Shamsi, Sonu Chand Thakur

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Abstract

Background: Alzheimer's disease (AD) is an advancing neurodegenerative disorder distinguished by the formation of amyloid plaques and neurofibrillary tangles in the human brain. Nevertheless, the lack of peripheral biomarkers that can detect the development of AD remains a significant limitation.

Objective: The main aim of this work was to discover the molecular markers associated with AD.

Methods: We conducted a comprehensive microarray analysis of gene expression data from hippocampus tissue in AD patients and control samples using three microarray datasets (GSE1297, GSE28146, and GSE29378) collected from Gene Expression Omnibus (GEO). The datasets were pre-processed and normalized, revealing 346 significant genes, 103 of which were upregulated and 243 downregulated. The PPI network of significant genes was constructed to detect the top 50 hub genes, which were then further analyzed using Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes pathway (KEGG), and GSEA, revealing 47 key genes involved in AD-related pathways. These key genes were then subjected to feed forward loop (FFL) motif analysis for the prediction of transcriptional factors (TFs) and microRNAs (miRNAs) mediated gene regulatory networks.

Results: The interaction of AD-associated TFs HNF4A, SPI1, EGR1, STAT3, and MYC and miRNAs hsa-miR-155-5p and hsa-miR-16-5p in the transcriptional and post-transcriptional events of 3 upregulated and 10 downregulated genes: H2AFZ, MCM3, MYO1C, AXIN1, CCND1, ETS2, MYH9, RELA, RHEB, SOCS3, TBL1X, TBP, TXNIP, and YWHAZ, respectively, has been identified. The miRNA/TF-mediated three types of the FFL motifs, i.e., miRNA-FFL, TF-FFL, and composite-FFL, were constructed, and seven common genes among these FFL were identified: CCND1, MYH9, SOCS3, RHEB, MYO1C, TXNIP, AXIN1, and TXNIP.

Conclusions: These findings may provide insights into the development of potential molecular markers for therapeutic management of AD.

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调查海马组织的基因表达数据集，发现阿尔茨海默病相关分子标记。

背景：阿尔茨海默病（AD）是一种以在人脑中形成淀粉样斑块和神经纤维缠结为特征的渐进性神经退行性疾病。然而，缺乏可检测 AD 发展的外周生物标志物仍然是一个重大的限制因素：本研究的主要目的是发现与 AD 相关的分子标记物：我们使用从基因表达总库（Gene Expression Omnibus，GEO）收集的三个微阵列数据集（GSE1297、GSE28146和GSE29378）对AD患者和对照样本海马组织的基因表达数据进行了全面的微阵列分析。这些数据集经过预处理和归一化后，发现了 346 个重要基因，其中 103 个基因上调，243 个基因下调。构建了重要基因的 PPI 网络，检测出前 50 个枢纽基因，然后使用基因本体（GO）术语、京都基因和基因组百科全书（KEGG）通路和 GSEA 对这些基因进行进一步分析，发现了 47 个参与 AD 相关通路的关键基因。然后对这些关键基因进行前馈环（FFL）主题分析，以预测转录因子（TF）和微RNA（miRNA）介导的基因调控网络：结果：AD相关TFs HNF4A、SPI1、EGR1、STAT3和MYC与miRNAs hsa-miR-155-5p和hsa-miR-16-5p在3个上调基因和10个下调基因的转录和转录后事件中相互作用：研究发现，H2AFZ、MCM3、MYO1C、AXIN1、CCND1、ETS2、MYH9、RELA、RHEB、SOCS3、TBL1X、TBP、TXNIP 和 YWHAZ 分别参与了 3 个上调基因和 10 个下调基因的转录和转录后事件。构建了由 miRNA/TF 介导的三种 FFL 模式，即 miRNA-FFL、TF-FFL 和复合-FFL，并发现了这些 FFL 中的七个共同基因：CCND1、MYH9、SOCS3、RHEB、MYO1C、TXNIP、AXIN1和TXNIP：这些发现可能为开发潜在的分子标记物以治疗AD提供启示。

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来源期刊

Journal of Alzheimer's Disease 医学-神经科学

CiteScore

6.40

自引率

7.50%

发文量

1327

审稿时长

2 months

期刊介绍： The Journal of Alzheimer''s Disease (JAD) is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer''s disease. The journal publishes research reports, reviews, short communications, hypotheses, ethics reviews, book reviews, and letters-to-the-editor. The journal is dedicated to providing an open forum for original research that will expedite our fundamental understanding of Alzheimer''s disease.