阿尔茨海默病发病前阶段的轻度认知障碍患者血浆miRNAs的生物信息学分析  

Bioinformatics analysis of plasma miRNAs in patients with mild cognitive impairment in the pre-Alzheimer’s stage

作　　者：姚永坤 卢香云[2] 韩吉铭 张婷[2] 邢文龙 张志强[1] 张桂青[1] YAO Yongkun;LU Xiangyun;HAN Jiming;ZHANG Ting;XING Wenlong;ZHANG Zhiqiang;ZHANG Guiqing(The First Affiliated Hospital of Medical College,Shihezi University,Shihezi,832000,Xinjiang,China;Medical College,Shihezi University,Shihezi,832000,Xinjiang,China)

机构地区：[1]石河子大学医学院第一附属医院,新疆石河子832000 [2]石河子大学医学院,新疆石河子832000

出　　处：《新疆医学》2022年第2期146-150,共5页Xinjiang Medical Journal

基　　金：石河子大学青年培育项目(项目编号:ZZZC201960A);国家自然科学基金(项目编号:31860279)。

摘　　要：目的 探讨阿尔茨海默病发病前阶段的轻度认知障碍患者血浆miRNAs表达及其靶基因在认知障碍中作用。方法 在GEO数据库获取与阿尔茨海默发病前阶段的轻度认知障碍患者表达谱的相关芯片数据,通过GEO2R分析出差异miRNAs并进行靶基因预测,再对预测的靶基因进行GO、KEGG及PPI分析。结果 按P<0.05,|log fold-change|≥2,筛选15个差异表达的miRNAs,其中上调miRNAs 10个,而下调miRNAs 5个;GO分析显示在表达上呈现差异的miRNAs靶基因主要参与核苷酸和核酸代谢、转运、基因表达调控等生物学过程;KEGG显示靶基因主要参与代谢通路、肿瘤信号通路、PI3K/AKT信号通路、钙信号通路及MAPK信号通路等重要通路;PPI分析结果发现,TP53、MAPK1、STAT3、PTPN11、EGFR等在PPI中处于核心地位。结论 表达上呈现异常的miRNAs在阿尔茨海默病发病前阶段的轻度认知障碍患者中挥着重要作用,为进一步探讨阿尔茨海默病发病前认知障碍发生、发展的分子机制提供依据,同时为筛选阿尔茨海默病发病前阶段的认知障碍早期分子标志物及开发靶向药物的提供新思路。Objective To investigate the expression of plasma mi RNAs and the role of their target genes in patients with mild cognitive impairment in the pre-stage of Alzheimer’s disease. Methods Microarray data related to the expression profile of patients with mild cognitive impairment in the pre-stage of Alzheimer’s disease were obtained from the GEO database. Differential mi RNAs were analyzed by GEO2R and target genes were predicted, and then GO, KEGG, and PPI analyses were performed for the predicted target genes.Results According to the P < 0.05, |log fold-change| ≥2 or higher, selection of mi RNAs in 15 differentially expressed, including up-regulated mi RNAs 10, down-regulated mi RNAs 5. GO analysis showed that mi RNAs target genes with different expression were mainly involved in biological processes such as nucleotide and nucleic acid metabolism, transport and gene expression regulation. KEGG showed that the target genes were mainly involved in metabolic pathways, tumor signaling pathways, PI3K/AKT signaling pathways,calcium signaling pathways, and MAPK signaling pathways. PPI analysis results found that TP53, MAPK1, STAT3, PTPN11, EGFR, and so on play a core role in PPI. Conclusions Abnormal expression of mi RNAs plays an important role in patients with mild cognitive impairment before stage. This study can provide the basis on further exploration about the molecular mechanism that cognitive impairment occurs before the onset of Alzheimer’s disease, at the same time it can provide new ideas for the screening early molecular markers of Alzheimer’s disease before the stage of cognitive impairment and development of targeted drugs.

关 键 词：阿尔茨海默病 认知障碍 MIRNAS 生物信息学 

分 类 号：R741[医药卫生—神经病学与精神病学]