基于mRNA-miRNA相互作用网络研究阿尔茨海默病机理

Alzheimer’s Disease Mechanism Exploration Based on mRNA-miRNA Interaction Network

本研究基于表达谱数据系统分析了阿尔茨海默病中的差异表达基因;进一步的GO和KEGG富集分析研究了差异表达基因参与的生物学功能和生物学过程;最后通过mRNA-miRNA相互作用网络,挖掘了阿尔茨海默病中的关键基因和调控机理。研究表明,990个基因在阿尔茨海默病中差异表达（p-value≤0.01,｜log FC｜≥2）,其中332个基因（33.5%）上调,658个基因（66.5%）下调。功能富集（GO）表明,差异基因参与了Regulation of macrophage activation、Myelin sheath和structural constituent of cytoskeleton等功能。KEGG通路富集分析表明,差异基因参与了,Synaptic vesicle cycle、PI3K-Akt signaling pathway、Nicotine addiction、Dopaminergic synapse和Retrograde endocannabinoid signaling等重要的生物学通路。最后,mRNA-miRNA相互作用网络鉴定了在阿尔茨海默病中6个关键的基因,包括TP53INP1、MET、MBNL3、CEBPB、GNAS和SMARCA4,其中TP53INP1和MET在前人的研究中有报道与阿尔茨海默病密切相关,MBNL3、CEBPB、GNAS和SMARCA4是新发现的一些基因。这些基因可能参与了阿尔茨海默病的发生和发展,可以作为其调控位点和药物靶点。

In this study, the differentially expressed genes in Alzheimer＇s disease（AD） were systematically analyzed based on expression profiles. Further, the biology functions of the DEGs were explored based on GO term and KEGG pathway enrichment analysis. Finally, the critical genes and regulation mechanism of AD were explored based on mRNA-miRNA interaction network. Results showed that 990 genes were differentially expressed in AD with p-value≤0.01 and ｜log FC｜≥2. Among those genes, 332 genes（33.5%） were up-regulated and 658 genes（66.5%）were down-regulated. GO results indicated that differentially expressed genes participated in regulation of macrophage activation,myelin sheath and structural constituent of cytoskeleton and so on. KEGG results showed that differentially expressed genes involved in Synaptic vesicle cycle, PI3 K-Akt signaling pathway, Nicotine addiction, Dopaminergic synapse and Retrograde endocannabinoid signaling and so on. Finally, six critical genes including TP53 INP1, MET, MBNL3, CEBPB, GNAS and SMARCA4 in AD were identified based on mRNA-miRNA interaction network. Among these genes, TP53 INP1 and MET have been reported in previous researches, and MBNL3, CEBPB, GNAS and SMARCA4 were discoveried in this study. The six critical genes probably involved in the occurrence and development of AD and can become the potential drug targets.