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Abstract：
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 MAPT and AP2M1, 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 (AP2M1), 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.
摘要：
阿尔茨海默病(Alzheimer’sdisease,AD)是一种进行性神经系统疾病,随着时间的推移而恶化。标志性疾病包括由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，和伴随神经胶质细胞增生的神经元损失。非编码RNA与相关的病理生理学密切相关，根据挂载数据。然而,这些ncRNAs的功能主要不清楚。环状RNA（circularRNAs）包括许多miRNA结合位点（miRNA反应元件，MRE),其作为miRNA海绵或竞争内源性RNA(ceRNA)起作用。这项研究的目的是观察环状RNA（circRNAs）和microRNAs（miRNAs）在阿尔茨海默病（AD）中作为可能的生物标志物的作用。基因表达综合(GEO)数据库用于获得阿尔茨海默病患者的表达谱(GSE5281、GSE122603、GSE97760、GSE150693、GSE1297和GSE161435)。通过初步的数据删除，163个基因具有显著差异，156个miRNAs具有显著差异，并鉴定了153个具有显著差异的circRNAs。然后，10个关键基因,由MAPT和AP2M1领导，由调解中心算法识别，通过cox回归模型鉴定出34个预后明显的miRNAs,数据库选择了16个关键circRNAs。为了发展竞争性内源性RNA(ceRNA)网络，使用hubcircRNAs和mRNAs。最后,对关键基因进行GO分析和临床数据验证。我们发现下调的circRNA（has_circ_002048）导致许多miRNA的表达增加，进一步抑制关键mRNA（AP2M1）的表达，导致阿尔茨海默病的病理学。这项工作的发现有助于更好地理解阿尔茨海默病中的circRNA-miRNA-mRNA调节过程。此外，本文发现的ncRNAs可能成为新的生物标志物和阿尔茨海默病药物开发的潜在靶标。
