鉴定阿尔茨海默病中的 lncRNA/circRNA-miRNA-mRNA ceRNA 网络。
Identification of a lncRNA/circRNA-miRNA-mRNA ceRNA Network in Alzheimer's Disease.
机构信息
Department of Basic Medicine, Hebei North University, 075000 Zhangjiakou, Hebei, China.
Department of Sports, Hebei North University, 075000 Zhangjiakou, Hebei, China.
出版信息
J Integr Neurosci. 2023 Oct 17;22(6):136. doi: 10.31083/j.jin2206136.
BACKGROUND
Alzheimer's disease (AD) occurs in the elderly and pre-elderly, characterized by decline of memory, cognitive dysfunction, impairment of learning capacity, and motor dysfunction. Recently a competitive endogenous RNA (ceRNA) network has been found to be related to AD progression, but there is still little understanding of the ceRNA regulatory network in AD. This study aims to explore the important regulatory mechanisms of ceRNA regulatory networks containing long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) in AD.
METHODS
Data from the gene expression omnibus (GEO) database were used for the analysis. To study enrichment function for the upregulated and downregulated mRNAs, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the Metascape database, respectively. Based on the STRING database and Cytoscape software 3.9.1, a protein-protein interaction (PPI) network was constructed. The hub genes in this network were identified utilizing the CytoHubba plugin in Cytoscape. The TargetScan, miRWalk, and miRDB were selected to calculate the regulatory interaction between miRNAs and the hub genes. LncRNAs were predicted using RNA22. Additionally, circRNA prediction was executed using the circBank database.
RESULTS
711 downregulated and 670 upregulated overlapping mRNAs were identified between AD and control samples. 32 downregulated and 340 upregulated miRNAs were obtained from AD samples compared with control samples. 78 upregulated and 205 downregulated circRNAs were screened. 275 upregulated lncRNAs and 209 downregulated lncRNAs were found between AD samples and control samples. The PPI network constructed consists of 1016 nodes and 13,946 edges. Ten hub genes were selected to identify target miRNAs and ceRNAs. On the basis of the ceRNA hypothesis, a circRNA/lncRNA-miRNA-mRNA network was established. It included five lncRNAs (TRHDE-AS1, SNHG10, OIP5-AS, LINC00926 and LINC00662), 26 circRNAs, five miRNAs (hsa-miR-3158-3p, hsa-miR-4435, hsa-let-7d-3p, hsa-miR-330-5p and hsa-miR-3605-3p), and ten mRNAs (, , , , , , , , , and ). and were found to be significantly associated with AD pathology in tau and Aβ line AD models by the AlzData database. The study discovered the significance of several lncRNA-miRNA-mRNA axes and circRNA-miRNA-mRNA axes that included and .
CONCLUSIONS
ceRNAs were found to be important regulators in the development of AD and provide potential biological therapy targets for AD management.
背景
阿尔茨海默病（AD）发生在老年人和老年前期，其特征是记忆下降、认知功能障碍、学习能力受损和运动功能障碍。最近发现竞争内源性 RNA（ceRNA）网络与 AD 进展有关，但对 AD 中的 ceRNA 调控网络仍知之甚少。本研究旨在探讨 AD 中包含长非编码 RNA（lncRNA）、环状 RNA（circRNA）、微小 RNA（miRNA）和信使 RNA（mRNA）的 ceRNA 调控网络的重要调控机制。
方法
使用基因表达综合数据库（GEO）中的数据进行分析。为了研究上调和下调 mRNA 的富集功能，使用 Metascape 数据库分别对基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析进行了分析。基于 STRING 数据库和 Cytoscape 软件 3.9.1，构建了一个蛋白质-蛋白质相互作用（PPI）网络。使用 Cytoscape 中的 CytoHubba 插件识别该网络中的枢纽基因。使用 TargetScan、miRWalk 和 miRDB 计算 miRNA 和枢纽基因之间的调控相互作用。使用 RNA22 预测 lncRNA。此外，使用 circBank 数据库执行 circRNA 预测。
结果
在 AD 与对照样本之间鉴定出 711 个下调和 670 个重叠的 mRNA。与对照样本相比，AD 样本中获得了 32 个下调和 340 个上调的 miRNA。筛选出 78 个上调和 205 个下调的 circRNA。在 AD 样本和对照样本之间发现了 275 个上调的 lncRNA 和 209 个下调的 lncRNA。构建的 PPI 网络包含 1016 个节点和 13946 个边。选择了 10 个枢纽基因来识别靶 miRNAs 和 ceRNAs。基于 ceRNA 假设，建立了一个 circRNA/lncRNA-miRNA-mRNA 网络。它包含 5 个 lncRNA（TRHDE-AS1、SNHG10、OIP5-AS、LINC00926 和 LINC00662）、26 个 circRNA、5 个 miRNA（hsa-miR-3158-3p、hsa-miR-4435、hsa-let-7d-3p、hsa-miR-330-5p 和 hsa-miR-3605-3p）和 10 个 mRNAs（,,,,,,,,, 和 ）。通过 AlzData 数据库，发现 和 在tau 和 Aβ 线 AD 模型中与 AD 病理学显著相关。该研究发现了一些 lncRNA-miRNA-mRNA 轴和 circRNA-miRNA-mRNA 轴的重要性，包括 和 。
结论
ceRNA 被发现是 AD 发展的重要调节剂，并为 AD 管理提供了潜在的生物治疗靶点。
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