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当代阿耳茨海默病研究

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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Research Article

ceRNA网络分析揭示AP-1转录因子成分是阿尔茨海默病的潜在生物标志物

卷 19, 期 5, 2022

发表于: 22 July, 2022

页: [387 - 406] 页: 20

弟呕挨: 10.2174/1567205019666220613142303

价格: $65

摘要

背景:阿尔茨海默病(AD)是一种影响老年人的进行性神经退行性疾病，其特征是认知功能下降。非编码RNAs参与AD的发病机制。 目的:利用6月龄淀粉样前体蛋白/早老蛋白1双转基因(APP/PS1)和野生型小鼠海马组织构建内源性RNA (ceRNA)网络，以寻找AD潜在的治疗靶点。 方法:应用limma R包分析APP/PS1和野生型小鼠海马区RNA-seq数据(GSE158995)，识别显著差异表达的mRNAs和circRNAs(分别为DEMs和DECs)。DEM基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析使用了Enrichr(https://maayanlab.cloud/Enrichr/)。使用ggcorrplot R包确定DEMs和DECs之间的相关性。使用STRING数据库和Cytoscape软件选择主要集群和集线器DEMs。使用miRTarbase和Starbase工具预测ceRNA相互作用，并使用ggallvial R软件包和Cytoscape软件构建。使用定量逆转录-聚合酶链反应(qRT-PCR)和Western blot对ceRNA网络进行验证。 结果:与野生型海马相比，APP/PS1中有198个DEMs和90个DECs表达差异。DEM GO分析显示，转录调控显著富集，可细分为转录调控、突触可塑性和蛋白质再折叠三个主要聚类。在转录调控簇中，AP-1转录因子组分充当枢纽基因。基于qRT-PCR和Western blot分析建立mmu_circ_0001787(circGLCE)/miR-339-5p/Junb和mmu_circ_0001899(circFAM120C)/ miR-181a-5p/Egr1 ceRNA网络。 结论:在AD小鼠模型中构建了两个AP-1转录因子成分相关的ceRNA网络circGLCE/miR- 339-5p/Junb和circFAM120C/miR-181a-5p/Egr1。这些ceRNA网络可能有助于AD的转录调节，并为AD的诊断和治疗提供潜在的生物标志物。

关键词: 阿尔茨海默病，环状RNA， microRNA，转录因子，ceRNA，基因本体论。

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