Chang Wan-Sheng, Wang Yong-Hong, Zhu Xiao-Tun, Wu Chuan-Jie
Department of Neurology, The Second People's Hospital of Liaocheng, Liaocheng Shandong, China (mainland).
Department of Neurosurgery, Xuanwu Hospital Capital Medical University, Beijing, China (mainland).
Med Sci Monit. 2017 Jun 4;23:2721-2731. doi: 10.12659/msm.905064.
BACKGROUND Our study aimed to identify key differentially expressed genes (DEGs) and miRNAs (DEmiRNAs) which can serve as potential biomarkers for diagnosis and therapy of Alzheimer's disease (AD). MATERIAL AND METHODS We performed miRNA and mRNA integrated analysis (MMIA) to identify DEGs and DEmiRNAs of AD. The AD-specific DEmiRNAs-targets interaction network was contrasted. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed. Q-RT-PCR was used to verify the expression of selected DEGs and DEmiRNAs. RESULTS We conducted MMIA of AD based on 1 miRNA dataset and 3 mRNA datasets derived from the Gene Expression Omnibus (GEO) database; 1759 DEGs and 12 DEmiRNAs were obtained. DEGs of AD were significantly enriched in Huntington's disease and AD. LRP1, CDK5R1, PLCb2, NDUFA4, and DLG4 were 5 DEGs regulated by 4 DEmiRNAs, including miR-26b-5p, miR-26a-5p, miR-107, and miR-103a-3p. These 4 miRNAs were the top 4 miRNAs covering most DEGs. According to the qRT-PCR results, the expression of PLCβ2, NDUFA4, DLG4, miR-107, and miR-103a-3p was consistent with our integrated analysis. CONCLUSIONS We concluded that LRP1, CDK5R1, PLCβ2, NDUFA4, and DLG4 may play a role in AD regulated by miR-26b-5p, miR-26a-5p, miR-107, and miR-103a-3p. Our findings will contribute to identification of biomarkers and new strategies for drug design for AD treatment.
背景 我们的研究旨在鉴定关键的差异表达基因（DEGs）和微小RNA（DEmiRNAs），它们可作为阿尔茨海默病（AD）诊断和治疗的潜在生物标志物。 材料与方法 我们进行了微小RNA和信使核糖核酸综合分析（MMIA）以鉴定AD的DEGs和DEmiRNAs。构建了AD特异性的DEmiRNAs-靶标相互作用网络。进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。采用定量逆转录聚合酶链反应（Q-RT-PCR）验证所选DEGs和DEmiRNAs的表达。 结果 我们基于来自基因表达综合数据库（GEO）的1个微小RNA数据集和3个信使核糖核酸数据集进行了AD的MMIA；获得了1759个DEGs和12个DEmiRNAs。AD的DEGs在亨廷顿病和AD中显著富集。低密度脂蛋白受体相关蛋白1（LRP1）、周期蛋白依赖性激酶5调节亚基1（CDK5R1）、磷脂酶Cβ2（PLCβ2）、烟酰胺腺嘌呤二核苷酸脱氢酶（泛醌）铁硫蛋白4（NDUFA4）和盘状球蛋白结构域蛋白4（DLG4）是受4种DEmiRNAs调控的5个DEGs，这4种DEmiRNAs包括miR-26b-5p、miR-26a-5p、miR-107和miR-103a-3p。这4种微小RNA是覆盖大多数DEGs的前4种微小RNA。根据定量逆转录聚合酶链反应结果，PLCβ2、NDUFA4、DLG4、miR-107和miR-103a-3p的表达与我们的综合分析一致。 结论 我们得出结论，LRP1、CDK5R1、PLCβ2、NDUFA4和DLG4可能在由miR-26b-5p、miR-26a-5p、miR-107和miR-103a-3p调控的AD中发挥作用。我们的研究结果将有助于鉴定生物标志物以及为AD治疗设计新的药物策略。
