河北医科大学学报 ›› 2021, Vol. 42 ›› Issue (10): 1128-1132,1148.doi: 10.3969/j.issn.1007-3205.2021.10.003

• • 上一篇    下一篇

遗忘型轻度认知功能损害血浆中竞争内源性RNA网络构建及分析

  

  1. 上海交通大学医学院附属精神卫生中心老年科,上海 200030
  • 出版日期:2021-10-25 发布日期:2021-10-28
  • 作者简介:张微(1994-),女,浙江嘉兴人,上海交通大学医学院附属精神卫生中心医师,医学硕士,从事神经认知障碍疾病诊治研究。
  • 基金资助:
    国家自然科学基金面上项目(81571298)

Construction and analysis of the competitive endogenous RNA network in amnestic mild cognitive impairment

  1. Department of Geriatrics, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200030, China
  • Online:2021-10-25 Published:2021-10-28

摘要: 目的 探讨阿尔茨海默病(Alzheimer′s disease,AD)轻度认知功能损害阶段(amentia mild cognitive impairment,aMCI)血浆中的非编码RNA(noncoding RNA,ncRNA)功能失调与AD的病理生理相关性,并探讨潜在的AD生物标志物和发病机制。
方法 纳入金标准诊断的aMCI受试者5例和正常对照组(normal control,NC)5例,应用微阵列技术分析aMCI和NC血浆中长链非编码RNA(long noncoding RNA,lncRNA)、微小RNA(microRNA,miRNA)和信使RNA(messenger RNA,mRNA)的表达谱,应用R软件筛选出差异表达的lncRNA、miRNA、mRNA,通过PicTar 2005、TargetScan 5.1和miRanda v5数据库对差异表达的RNA的关系进行分析,建立以上调lncRNA为中心的竞争内源性RNA(competing endogenous RNA,ceRNA)网络,并对其中相关差异表达的mRNA进行基因本体论功能富集和京都基因与基因组百科全书通路富集分析。
结果 在外周血浆中总共筛选出lncRNA 287个、miRNA 46个和mRNA 208个在aMCI和NC的表达差异有统计学意义(P<0.05),分别有lncRNA3个、 miRNA5个和mRNA7个参与构建了遗忘型轻度认知功能损害ceRNA调控网络。GO和KEGG结果显示差异表达mRNAs主要在RNA代谢过程、细胞质应激颗粒、转录调控因子活性等生物学过程,单纯疱疹感染通路、催产素信号通路和叶酸合成通路上显著聚集。
结论 不同的ncRNA参与AD的发病机制,构建的ceRNA网络有助于增进对AD发病分子生物学机制的认识,ncRNAs可能成为AD诊断的生物标志物和治疗干预的新靶点。


关键词: 阿尔茨海默病, RNA, 未翻译, RNA, 信使

Abstract: Objective To investigate the correlation of non-coding RNA(ncRNA) dysfunction in plasma of patients with Alzheimer′s disease(AD) at the stage of amnestic mild cognitive impairment(aMCI) and the pathophysiology of AD and to explore the potential biomarkers and mechanisms underlying AD. 
Methods Flve subjects with aMCI who met the golden standard for diagnosis and five normal controls(NC) were enrolled. Microarray analysis technology was used to analyze the expression profiles of long noncoding RNA(lncRNA), microRNA(miRNA) and messenger RNA(mRNA) in plasma of aMCI and NC. R software was used to screen out differentially expressed lncRNA, miRNA and mRNA, and PicTar 2005, TargetScan 5.1 and miRanda v5 database were used to detect the relationship between RNAs, to establish a competitive endogenous RNA(ceRNA) network. Gene Ontology(GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were conducted for the differentially expressed mRNAs. 
Results A total of 287 lncRNAs, 46 miRNAs and 208 mRNAs were differentially expressed in the peripheral plasma between aMCI and NC(P<0.05), in which 3 lncRNAs, 5 miRNAs and 7 mRNAs participated in the construction of ceRNA regulatory network. The results of GO and KEGG showed that differentially expressed mRNAs were mainly accumulated in biological processes such as RNA metabolism, cytoplasmic stress granules, transcriptional regulatory factor activities, herpes simplex infection pathway, oxytocin signaling pathway, and folic acid synthesis pathway. 
Conclusion Different ncRNAs are involved in the pathogenesis of AD. The constructed ceRNA network helps to improve the understanding of the molecular biology of AD, and ncRNAs may become biomarkers for AD diagnosis and new targets for therapeutic intervention.


Key words: Alzheimer disease, RNA, Untranslated, RNA, Messenger