Teaching Laboratory Center of Medicine and Life Science, Tongji University School of Medicine, Shanghai, 200092, China.
Department of Neurology, The Seventh People's Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China.
Neurochem Res. 2021 Apr;46(4):964-979. doi: 10.1007/s11064-020-03215-8. Epub 2021 Feb 13.
Alzheimer's disease (AD) is a growing health concern worldwide. MicroRNAs (miRNAs) have been extensively studied in many diseases, including AD. To identify differentially expressed miRNAs (DEmiRNAs) and genes specific to AD, we used bioinformatic analyses to investigate candidate miRNA-mRNA pairs involved in the pathogenesis of AD. We focused on differentially expressed genes (DEGs) that are targets of DEmiRNAs. The GEO2R tool and the HISAT2-DESeq2 software were used to identify DEmiRNAs and DEGs. Bioinformatic tools available online, such as TAM and the Database for Annotation, Visualization and Integrated Discovery (DAVID), were used to perform functional annotation and enrichment analysis. Targets of miRNAs were predicted using the miRTarBase. The Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape, which are available online, were utilized to construct protein-protein interaction (PPI) networks and identify hub genes. Furthermore, transcription factors (TFs) encoded by the DEGs were predicted using the TransmiR database and TF-miRNA-mRNA networks were constructed. Finally, the expression profile of a hub gene in peripheral blood mononuclear cells was compared between healthy individuals and AD patients. We identified 26 correlated miRNA-mRNA pairs. In the parietal lobe, miRNA-mRNA pairs involved in protein folding were enriched, and in the frontal lobe, miRNA-mRNA pairs involved in synaptic transmission, abnormal protein degradation, and apoptosis were enriched. In addition, HSP90AB1 in peripheral blood mononuclear cells was found to be significantly downregulated in AD patients, and this was consistent with its expression profile in the parietal lobe of AD patients. Our results provide brain region-specific changes in miRNA-mRNA associations in AD patients, further our understanding of potential underlying molecular mechanisms of AD, and reveal promising diagnostic and therapeutic targets for AD.
阿尔茨海默病（AD）是全球日益严重的健康问题。microRNAs（miRNAs）在许多疾病中，包括 AD 中都得到了广泛的研究。为了确定 AD 特有的差异表达 miRNA（DEmiRNAs）和基因，我们使用生物信息学分析来研究涉及 AD 发病机制的候选 miRNA-mRNA 对。我们专注于 DEmiRNAs 的靶标差异表达基因（DEGs）。使用 GEO2R 工具和 HISAT2-DESeq2 软件来识别 DEmiRNAs 和 DEGs。在线可用的生物信息学工具，如 TAM 和 Database for Annotation, Visualization and Integrated Discovery（DAVID），用于进行功能注释和富集分析。使用 miRTarBase 预测 miRNA 的靶标。在线可用的 Search Tool for the Retrieval of Interacting Genes（STRING）和 Cytoscape 用于构建蛋白质-蛋白质相互作用（PPI）网络和识别枢纽基因。此外，使用 TransmiR 数据库预测 DEGs 编码的转录因子（TFs），并构建 TF-miRNA-mRNA 网络。最后，比较了健康个体和 AD 患者外周血单核细胞中枢纽基因的表达谱。我们鉴定了 26 个相关的 miRNA-mRNA 对。在顶叶中，富集了涉及蛋白质折叠的 miRNA-mRNA 对，而在额叶中，富集了涉及突触传递、异常蛋白降解和细胞凋亡的 miRNA-mRNA 对。此外，在外周血单核细胞中发现 HSP90AB1 在 AD 患者中显著下调，这与 AD 患者顶叶中的表达谱一致。我们的研究结果提供了 AD 患者中 miRNA-mRNA 关联的脑区特异性变化，进一步加深了我们对 AD 潜在分子机制的理解，并揭示了 AD 的有前途的诊断和治疗靶点。
