Neurology Department, Shanghai Tianyou Hospital, Shanghai 200040, P.R. China.
Mol Med Rep. 2020 Aug;22(2):1053-1062. doi: 10.3892/mmr.2020.11162. Epub 2020 May 20.
Alzheimer's disease (AD) is a progressive neurodegenerative disease, which is considered the most common type of dementia worldwide. The aim of the present study was to identify key microRNAs (miRNAs/miRs) and mRNAs affecting the pathogenesis of AD, which may be developed as promising biomarkers for the early diagnosis or targeted therapy of patients with AD. Integrative analysis was performed on 12 representative miRNA datasets and three mRNA datasets of the blood from patients with AD, in order to identify differentially expressed (DE)miRNAs and DEmRNAs. Subsequently, the miRWalk database was used to identify the potential miRNA‑mRNA interactions among DEmiRNAs and DEmRNAs, and an AD‑specific miRNA‑mRNA network was constructed using Cytoscape software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to assess the target mRNAs of DEmiRNAs. A total of 37 DEmiRNAs and 2,011 DEmRNAs were identified between AD and normal control samples. In addition, 853 high confidence miRNA‑mRNA interactions were identified and subsequently used to construct the AD specific miRNA‑mRNA network. A total of five miRNAs, including hsa‑miR‑93, hsa‑miR‑26b, hsa‑miR‑34a, hsa‑miR‑98‑5p and hsa‑miR‑15b‑5p were identified as the key nodes in the miRNA‑mRNA network by topological analysis. Functional enrichment analysis demonstrated that the target mRNAs of DEmiRNAs were enriched in AD‑associated pathways, such as the 'neurotrophin signaling pathway' and 'insulin signaling pathway'. Taken together, the results of the present study provide novel insights into the molecular mechanisms underlying AD and contribute to the identification of biomarkers and novel strategies for drug design for AD treatment.
阿尔茨海默病(AD)是一种进行性神经退行性疾病,被认为是全球最常见的痴呆症类型。本研究旨在鉴定影响 AD 发病机制的关键 microRNAs(miRNAs/miRs)和 mRNAs,这些可能成为 AD 患者早期诊断或靶向治疗的有希望的生物标志物。对 12 个具有代表性的 miRNA 数据集和 3 个 AD 患者血液 mRNA 数据集进行综合分析,以鉴定差异表达(DE)miRNAs 和 DEmRNAs。随后,使用 miRWalk 数据库鉴定 DEmiRNAs 和 DEmRNAs 之间潜在的 miRNA-mRNA 相互作用,并使用 Cytoscape 软件构建 AD 特异性 miRNA-mRNA 网络。通过基因本体论和京都基因与基因组百科全书通路富集分析评估 DEmiRNAs 的靶 mRNAs。在 AD 与正常对照样本之间共鉴定出 37 个 DEmiRNAs 和 2011 个 DEmRNAs。此外,鉴定出 853 个高置信度的 miRNA-mRNA 相互作用,并随后用于构建 AD 特异性 miRNA-mRNA 网络。通过拓扑分析,共鉴定出 5 个 miRNA,包括 hsa-miR-93、hsa-miR-26b、hsa-miR-34a、hsa-miR-98-5p 和 hsa-miR-15b-5p,作为 miRNA-mRNA 网络中的关键节点。功能富集分析表明,DEmiRNAs 的靶 mRNAs 富集在 AD 相关通路中,如“神经递质信号通路”和“胰岛素信号通路”。综上所述,本研究结果为 AD 的分子机制提供了新的见解,并有助于鉴定 AD 生物标志物和新型药物设计策略。