上海交通大学学报（医学版）

上海交通大学学报(医学版) ›› 2020, Vol. 40 ›› Issue (09): 1174-1183.doi: 10.3969/j.issn.1674-8115.2020.09.003

• 论著·基础研究 • 上一篇    下一篇

阿尔茨海默病引起的轻度认知功能损害的微小RNA表达谱的生物信息学分析

何海宁，张 微，严 峰，史琰琛，王静华，肖世富#，王 涛#   

  1. 上海交通大学医学院附属精神卫生中心老年精神科，上海交通大学阿尔茨海默病诊治中心，上海 200030
  • 出版日期:2020-09-28 发布日期:2020-11-04
  • 通讯作者: 王 涛，电子信箱：wtshhwy@163.com。肖世富，电子信箱：xiaoshifu@msn.com。#为共同通信作者。
  • 作者简介:何海宁（1995—），女，硕士生；电子信箱：haininghe0425@163.com。
  • 基金资助:
    上海市教育委员会高峰高原学科建设计划（20172029）；国家自然科学基金（81571298）；上海市浦江人才计划 （17PJD038）；上海市卫生和计划生育委员会优秀学科带头人人才培养计划（“新百人计划”）（2017BR054）；上海市精神卫生中心临床研究中心重点项目（CRC2019ZD03, CRC2017ZD02）。

Bioinformatics analysis of miRNAs in mild cognitive impairment due to Alzheimer's disease

HE Hai-ning, ZHANG Wei, YAN Feng, SHI Yan-chen, WANG Jing-hua, XIAO Shi-fu#, WANG Tao#   

  1. Alzheimer's Disease and Related Disorders Center, Department of Geriatric Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
  • Online:2020-09-28 Published:2020-11-04
  • Supported by:
    Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support (20172029); National Nature Science Foundation of China (81571298); Shanghai Pujiang Talent Plan (17PJD038); New Hundred Talents Program (Outstanding Academic Leader) from Shanghai Municipal Commission of Health and Family Planning (2017BR054); Major Project of Clinical Research Center, Shanghai Mental Health Center (CRC2019ZD03, CRC2017ZD02).

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摘要： 目的·分析阿尔茨海默病（Alzheimer's disease，AD）所致轻度认知功能损害（mild cognitive impairment，MCI）患者的血浆微小RNA（microRNA，miRNA）表达谱，并探讨AD所致MCI在遗传调控水平上的发病机制。方法·纳入5例AD所致MCI患者和5例对照受试者，应用miRNA芯片测序技术分析血浆miRNA表达谱。采用TargetScan 7.2数据库分析显著上调miRNA的靶基因。采用Cytoscape软件分析显著上调miRNA的miRNA-基因相互作用网络，筛选关键miRNA。运用R语言对关键miRNA的靶基因进行基因本体数据库（GO）富集分析和京都基因与基因组百科全书（KEGG）通路分析。结果·AD所致MCI患者的血浆中存在13个显著上调的miRNA，其中有5个是核心调控网络中的关键miRNA，其靶标基因主要参与突触可塑性调节、Wnt信号通路、突触间囊泡转运和突触间囊泡定位等生物学过程，并调控Ras信号通路、丝裂原活化蛋白激酶信号通路和糖酵解/糖异生等通路。结论·AD所致MCI患者血浆中5个上调的miRNA可能作为关键调控因素参与AD相关的病理进程，或可成为诊断AD所致MCI的潜在生物学标志物。

关键词: 阿尔茨海默病, 轻度认知功能损害, 微小RNA, 生物信息学

Abstract:

Objective · To analyze the expression profile of plasma microRNA (miRNA) in patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) by bioinformatics method, and explore its pathogenesis at the level of genetic regulation. Methods · Five MCI patients due to AD and five control participants were recruited. The plasma miRNA expression profiles were analyzed by miRNA microarray sequencing. Target genes of significantly up-regulated miRNAs were detected by TargetScan 7.2 database. The miRNA-gene interaction network of significantly up-regulated miRNAs was established by Cytoscape software, and the key miRNAs of the network were analyzed. The target genes of key miRNAs were analyzed by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis using R packages. Results · There are 13 up-regulated miRNAs in the plasma of MCI patients due to AD, and 5 of them were key miRNAs in miRNA-gene interaction network. Target genes of these miRNAs were mainly involved in biological process such as synaptic plasticity regulation, Wnt signaling pathway, synaptic vesicle transport and synaptic vesicle localization, as well as Ras signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway and glycolysis/gluconeogenesis pathway. Conclusion · Five up-regulated miRNAs in plasma of MCI due to AD may be the main regulators involved in the pathological mechanism of AD, which can be used as potential biomarkers for diagnosis of MCI due to AD.

Key words: Alzheimer's disease (AD), mild cognitive impairment (MCI), microRNA (miRNA), bioinformatics

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