Besli Nail, Sarikamis Bahar, Kalkan Cakmak Rabia, Kilic Ulkan
Department of Medical Biology, University of Health and Sciences Institute of Health Sciences, İstanbul, Turkey.
Department of Medical Biology, University of Health and Sciences Institute of Health Sciences, İstanbul, Turkey; Department of Medical Biology, University of Health Sciences Hamidiye Faculty of Medicine, İstanbul, Turkey.
Eurasian J Med. 2023 Oct;55(3):218-227. doi: 10.5152/eurasianjmed.2023.23029.
Alzheimer's disease is a neurodegenerative sickness and increasing with age throughout the world. A substantial body of evidence suggests the role of exosomal noncoding ribonucleic acids in the development of Alzheimer's disease, but the regulatory mechanisms mediated by these noncoding ribonucleic acids remain extensively unknown. Using plasma samples from Alzheimer's disease patients, this study explored the exosomal circular ribonucleic acid-microribonucleic acid profiles.
The ArrayExpress platform was used to convey data from 3 samples from each group (healthy, mild cognitive impairment, and Alzheimer's disease). Using plasma exosomes, differentially expressed microribonucleic acids and differentially expressed circular ribonucleic acids were compared between the Alzheimer's disease and mild cognitive impairment groups. Afterward, to define pathways, gene ontologies, and networks, differentially expressed microribonucleic acids and differentially expressed circular ribonucleic acids common to both mild cognitive impairment and Alzheimer's disease groups were analyzed. Eventually, the selection of hub genes and protein-protein interaction network was analyzed.
A total of common 19 (7 upregulated and 12 downregulated) differentially expressed microribonucleic acids and 24 differentially expressed circular ribonucleic acids were recognized. A total of 4559 target genes were predicted for upregulated differentially expressed microribonucleic acids, while 6504 target genes were identified for downregulated differentially expressed microribonucleic acids, and most of the target genes involved in the phosphoinositide 3-kinases-Akt pathway and that were mostly regulated by hsa-mir-374a-3p, mir-196a-5p, let-205-5p, mir-185-3p, mir-374a-5p, mir-615-3p, let-7c-5p, mir-185-5p. Additionally, 9 hub genes (HSP90AA, ACTB, MAPK1, GSK3B, CCNE2, CDK6, AKT1, IGF1R, CCND1) were revealed as the genes considerably related to Alzheimer's disease by a protein-protein interaction network using the cytohubba in Cytoscape software.
Our findings provide a new perspective on how microribonucleic acids could connect with circular ribonucleic acids in the pathogenesis of Alzheimer's disease.
阿尔茨海默病是一种神经退行性疾病，在全球范围内随着年龄增长而增加。大量证据表明外泌体非编码核糖核酸在阿尔茨海默病的发展中起作用，但这些非编码核糖核酸介导的调控机制仍广泛未知。本研究使用阿尔茨海默病患者的血浆样本，探索了外泌体环状核糖核酸-微小核糖核酸图谱。
使用ArrayExpress平台传达每组（健康、轻度认知障碍和阿尔茨海默病）3个样本的数据。使用血浆外泌体，比较了阿尔茨海默病组和轻度认知障碍组之间差异表达的微小核糖核酸和差异表达的环状核糖核酸。之后，为了定义途径、基因本体和网络，分析了轻度认知障碍组和阿尔茨海默病组共有的差异表达微小核糖核酸和差异表达环状核糖核酸。最终，分析了枢纽基因的选择和蛋白质-蛋白质相互作用网络。
共识别出19种常见的（7种上调和12种下调）差异表达微小核糖核酸和24种差异表达环状核糖核酸。上调的差异表达微小核糖核酸共预测到4559个靶基因，而下调的差异表达微小核糖核酸鉴定出6504个靶基因，大多数靶基因参与磷脂酰肌醇3-激酶-Akt途径，且大多受hsa-mir-374a-3p、mir-196a-5p、let-205-5p、mir-185-3p、mir-374a-5p、mir-615-3p、let-7c-5p、mir-185-5p调控。此外，使用Cytoscape软件中的cytohubba通过蛋白质-蛋白质相互作用网络揭示了9个枢纽基因（HSP90AA、ACTB、MAPK1、GSK3B、CCNE2、CDK6、AKT1、IGF1R、CCND1）为与阿尔茨海默病显著相关的基因。
我们的研究结果为微小核糖核酸在阿尔茨海默病发病机制中如何与环状核糖核酸相互联系提供了新的视角。
