摘要
目的本研究对比乙酰胆碱受体抗体阳性重症肌无力患者(AchR-MG)和正常对照组外周血单个核细胞miRNA,预测对AchR-MG发病可能产生影响的通路,为进一步探讨发病机制打下基础。方法采用病例对照研究方法,基于高通量测序,筛选了AchR-MG特异性表达的miRNA。利用TargetScan、miRanda进行靶基因交叉预测,利用基因条目(GO)和京都基因与基因组百科全书(KEGG)进行富集分析。结果共筛选出差异性miRNA 28种,其中上调17种,下调11种。差异最显著的前5个为:mmu-miR-3968、miR-4785、miR-210-3p、miR-664a-3p、miR-2277-5p。miR-4785预测到METTL22、TMEM38A、ZNF324、ITGB4、CDC34等395种靶基因。最终识别了319条GO term(P<0.01),获得了119个的风险通路(P<0.05)。结论AchR-MG特异性表达miR-4785、miR-210-3p、miR-664a-3p、miR-2277-5p等28种miRNA。以Wnt信号通路为代表的多种通路可能参与AchR-MG的发病。
Objective To investigate the difference in the expression profile of microRNAs(miRNAs)in peripheral blood mononuclear cells(PBMCs)between patients with myasthenia gravis with acetylcholine receptor antibodies(AchR-MG)and healthy controls,predict the possible pathways involved in the development of AchR-MG,and to lay a foundation for further research on the pathogenesis of AchR-MG.Methods A case-control study was performed to screen out specifically expressed miRNAs in AchR-MG patients based on high-throughput sequencing.TargetScan and miRanda were used for cross-prediction of target genes,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed.Results A total of 28 differentially expressed miRNAs were screened out,among which 17 were upregulated and 11 were downregulated.The top 5 differentially expressed miRNAs were mmu-miR-3968,miR-4785,miR-210-3p,miR-664a-3p,and miR-2277-5p.A total of 395 target genes,such as METTL22,TMEM38A,ZNF324,ITGB4,and CDC34,were predicted for miR-4785.A total of 319 GO terms were identified(P<0.01),and 119 risk pathways were obtained(P<0.05).Conclusions A total of 28 specifically expressed miRNAs are found in AchR-MG,including miR-4785,miR-210-3p,miR-664a-3p,and miR-2277-5p.Multiple pathways,including the Wnt signaling pathway,may be involved in the pathogenesis of AchR-MG.
作者
谭颖
管宇宙
朱立
崔丽英
TAN Ying;GUAN Yu-Zhou;ZHU Li;CUI Li-Ying(Department of Neurology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,Beijing 100010,China)
出处
《国际神经病学神经外科学杂志》
2019年第6期589-595,共7页
Journal of International Neurology and Neurosurgery
基金
首都临床特色应用研究(Z181100001718145)
