APP/PS1转基因小鼠脑组织环状RNA的差异表达谱及相关ceRNA构建  

Differential expression profile of circular RNA in brain tissue of APP/PS1 transgenic mice and its related ceRNA construction

作　　者：马琳秋 侯明亮 李金平 杨红岩 廖旗荣 李小雄 洪文娟 周华东 MA Linqiu;HOU Mingliang;LI Jinping;YANG Hongyan;LIAO Qirong;LI Xiaoxiong;HONG Wenjuan;ZHOU Huadong(Department of Neurology,The First Affiliated Hospital of Bengbu Medical University,Bengbu Anhui 233004;Department of Neurology,Army Medical Center of PLA,Chongqing 400020,China)

机构地区：[1]蚌埠医科大学第一附属医院神经内科,安徽蚌埠233004 [2]陆军特色医学中心神经内科,重庆400020

出　　处：《蚌埠医学院学报》2024年第1期1-6,共6页Journal of Bengbu Medical College

基　　金：国家自然科学基金项目(81771177)。

摘　　要：目的:探讨阿尔茨海默病(AD)模型小鼠脑组织中环状RNA(circRNA)的差异表达谱,构建circRNA-miRNA-mRNA调控网络,明确circRNA在AD发生中的调控机制。方法:采用基因芯片技术检测APP/PS1转基因AD模型小鼠大脑中circRNA的差异表达,对差异circRNA进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析,采用实时定量聚合酶链反应验证随机选取的5个差异表达的circRNA,构建circRNA-miRNA-mRNA,进行AD靶基因功能预测分析。结果:共筛选出52个差异表达的circRNA,其中28个上调,24个下调。GO和KEGG的富集分析结果显示,差异表达的circRNA的亲本基因主要参与神经系统发育、蛋白质结合、RNA运输、调控干细胞多能性的信号通路和Hippo信号通路。生物学信息分析成功构建circRNA-miRNA-mRNA的竞争性内源(ceRNA)网络,显示这些靶基因富集的功能可能通过小分子结合、浆膜、cAMP信号通路和Rap1信号通路发挥作用。结论:AD模型小鼠大脑中存在多种差异表达的circRNA,这些差异基因可能通过circRNA-miRNA-mRNA调节网络参与AD发生的分子调控。Objective:To explore the differential expression profile of circular RNA(circRNA)in brain tissue of Alzheimer′s disease(AD)model mouse,to construct circRNA-miRNA-mRNA regulatory network,and to clarify the regulatory mechanism of circRNA in the occurrence of AD.Methods:The differential expression of circRNA in the brain of APP/PS1 transgenic AD model mice was analyzed by gene microarray.Gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG)pathway analysis were performed on the differential circRNAs.Real-time quantitative polymerase chain reaction was used to verify the randomly selected 5 differentially expressed circRNAs,and circRNA-miRNA-mRNA was constructed to perform AD target gene function prediction analysis.Results:A total of 52 differentially expressed circRNAs were screened,of which 28 were up-regulated and 24 were down-regulated.The enrichment analysis results of GO and KEGG showed that the differentially expressed parental genes of circRNAs were mainly involved in nervous system development,protein binding,RNA transport,signaling pathways regulating stem cell pluripotency,and Hippo signaling pathways.Biological information was used to analyze the successfully constructed competing endogenous RNA(ceRNA)network of circRNA-miRNA-mRNA,indicating that the enriched functions of these target genes might play a role through small molecule binding,plasma membrane,cAMP signaling pathway,and Rap1 signaling pathway.Conclusions:There are various differentially expressed circRNAs in the brain of AD model mice,and these differentially expressed genes may be involved in the molecular regulation of AD occurrence through the circRNA-miRNA-mRNA regulatory network.

关 键 词：阿尔茨海默病 环状RNA 微小RNA circRNA-miRNA-mRNA调节网络 

分 类 号：R737.9[医药卫生—肿瘤]