Zhang Qi, Chen Bishuang, Yang Ping, Wu Jipan, Pang Xinping, Pang Chaoyang
School of Computer Science, Sichuan Normal University, Chengdu, China.
West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China.
Front Genet. 2022 Nov 18;13:1049786. doi: 10.3389/fgene.2022.1049786. eCollection 2022.
Alzheimer's disease (AD) is a progressive neurological disease that worsens with time. The hallmark illnesses include extracellular senile plaques caused by β-amyloid protein deposition, neurofibrillary tangles caused by tau protein hyperphosphorylation, and neuronal loss accompanying glial cell hyperplasia. Noncoding RNAs are substantially implicated in related pathophysiology, according to mounting data. However, the function of these ncRNAs is mainly unclear. Circular RNAs (circRNAs) include many miRNA-binding sites (miRNA response elements, MREs), which operate as miRNA sponges or competing endogenous RNAs (ceRNAs). The purpose of this study was to look at the role of circular RNAs (circRNAs) and microRNAs (miRNAs) in Alzheimer's disease (AD) as possible biomarkers. The Gene Expression Omnibus (GEO) database was used to obtain an expression profile of Alzheimer's disease patients (GSE5281, GSE122603, GSE97760, GSE150693, GSE1297, and GSE161435). Through preliminary data deletion, 163 genes with significant differences, 156 miRNAs with significant differences, and 153 circRNAs with significant differences were identified. Then, 10 key genes, led by and , were identified by the mediation center algorithm, 34 miRNAs with obvious prognosis were identified by the cox regression model, and 16 key circRNAs were selected by the database. To develop competitive endogenous RNA (ceRNA) networks, hub circRNAs and mRNAs were used. Finally, GO analysis and clinical data verification of key genes were carried out. We discovered that a down-regulated circRNA (has_circ_002048) caused the increased expression of numerous miRNAs, which further inhibited the expression of a critical mRNA (), leading to Alzheimer's disease pathology. The findings of this work contribute to a better understanding of the circRNA-miRNA-mRNA regulating processes in Alzheimer's disease. Furthermore, the ncRNAs found here might become novel biomarkers and potential targets for the development of Alzheimer's drugs.
阿尔茨海默病(AD)是一种随着时间推移而恶化的进行性神经疾病。其标志性病变包括由β-淀粉样蛋白沉积引起的细胞外老年斑、由tau蛋白过度磷酸化引起的神经原纤维缠结以及伴随胶质细胞增生的神经元丢失。越来越多的数据表明,非编码RNA在相关病理生理学中起着重要作用。然而,这些非编码RNA的功能主要尚不清楚。环状RNA(circRNAs)包含许多微小RNA结合位点(微小RNA反应元件,MREs),其作为微小RNA海绵或竞争性内源性RNA(ceRNAs)发挥作用。本研究的目的是探讨环状RNA(circRNAs)和微小RNA(miRNAs)在阿尔茨海默病(AD)中作为潜在生物标志物的作用。利用基因表达综合数据库(GEO)获取阿尔茨海默病患者的表达谱(GSE5281、GSE122603、GSE97760、GSE150693、GSE1297和GSE161435)。通过初步数据删除,鉴定出163个有显著差异的基因、156个有显著差异的微小RNA和153个有显著差异的环状RNA。然后,通过中介中心算法鉴定出以 和 为首的10个关键基因,通过cox回归模型鉴定出34个具有明显预后的微小RNA,并通过数据库选择出16个关键环状RNA。为构建竞争性内源性RNA(ceRNA)网络, 使用了枢纽环状RNA和信使核糖核酸。最后,对关键基因进行了基因本体(GO)分析和临床数据验证。我们发现一个下调的环状RNA(has_circ_002048)导致众多微小RNA的表达增加,这进一步抑制了一个关键信使核糖核酸()的表达,从而导致阿尔茨海默病病理改变。这项工作的发现有助于更好地理解阿尔茨海默病中环状RNA-微小RNA-信使核糖核酸的调控过程。此外,在此发现的非编码RNA可能成为阿尔茨海默病药物开发的新型生物标志物和潜在靶点。