ATRNL1在阿尔茨海默病中的基因功能分析及ceRNA网络预测

Gene function analysis of ATRNL1 and ceRNA network construction in Alzheimer’s disease

目的:通过对ATRNL1基因的生物信息学分析,明确其在阿尔茨海默病(Alzheimer’s disease,AD)中的作用。方法:通过高通量基因表达(gene expression omnibus,GEO)数据库下载AD芯片数据GSE36980、GSE1297和GSE28146,利用3个独立数据验证ATRNL1在AD中的差异表达情况,并计算Pearson相关系数分析ATRNL1与临床信息的相关性;使用GSE1297数据筛选ATRNL1共表达基因并使用clusterProfiler程序包进行基因功能注释,包括基因本体论(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析;为研究ATRNL1差异表达的调控机制,使用multiMiR程序包下载miRNA相互作用数据,根据竞争性内源RNA(competing endogenous RNAs,ceRNA)的调控机制构建ATRNL1-miRNA-mRNA调控网络。结果:3个独立芯片数据中ATRNL1在AD中表达明显下降(P<0.05);ATRNL1表达与PMI评分明显相关(P<0.05),与简易智力状态检查量表(mini-mental status examination,MMSE)评分明显相关(P<0.001),与神经元神经原纤维缠结(neurofibrillary tangles,NFT)评分明显相关(P<0.05);ATRNL1共表达基因的富集分析发现,信号释放生物学过程(GO:0023061)、突触小泡周期(hsa04721)、γ-氨基丁酸能突触(hsa04727)与ATRNL1明显相关;构建的ATRNL1-miRNA-mRNA调控网络发现,MOAP1、WDR47、REEP1等基因很可能与hsa-miR-192-5p竞争性调控ATRNL1表达,与ATRNL1构成ceRNA。结论:首次发现ATRNL1可能通过调控突触的信号传递以及影响γ-氨基丁酸能突触,影响AD发病,ATRNL1可能通过hsamiR-192-5p与MOAP1构成ceRNA。

Objective:To investigate and identify gene ATRNL1 function in Alzheimer’s disease(AD).Methods:Microarray data GSE36980,GSE1297,and GSE28146 were downloaded from gene expression omnibus(GEO)database.ATRNL1differential expression of AD in Alzheimer’s disease was validated by 3 independent datasets.Meanwhile,Pearson correlation test between ATRNL1 expression and clinical data were performed.ATRNL1 co-expression gene screening and function enrichment analysis was performed by clusterProfiler,which included gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)annotation.To further illustrate ATRNL1molecule interaction detail,multiMiR package was used todownload miRNA interaction,finally ATRNL1-miRNA-mRNAnetwork was constructed for competing endogenous RNAs(ceRNA)identification of ATRNL1.Results:Three isolateddatasets showed ATRNL1 was significantly decreased(P<0.05).ATRNL1 expression was significantly correlated with PMI(P<0.05),mini-mental status examination(MMSE)(P<0.001),and neurofibrillary tangles(NFT)(P<0.05).ATRNL1 co-expression genes enrichment analysis showed that the biological process of signal release(GO:0023061),synaptic vesicle cycle(hsa04721),GABAergic synapse(hsa04727)weresignificantly related to ATRNL1.The constructed ATRNL1-miRNA-mRNA regulatory network found that MOAP1,WDR47,and REEP1 were found as ceRNA by competing hsa-miR-192-5p with ATRNL1.Conclusion:It is discovered forthe first time that ATRNL1 may affect AD occurrence through synapse signal release and GABAergic synapse,and moreimportantly ATRNL1 may function as ceRNA with MOAP1 by competing hsa-miR-192-5p.