重症肌无力患者血浆外泌体microRNA表达谱的初步研究

Preliminary study on microRNA expression profile of plasma exosomes in patients with myasthenia gravis

目的:分析重症肌无力患者(MG)血浆外泌体microRNA(miRNA)的表达谱,寻找诊断重症肌无力的潜在生物标志物。方法:应用深度测序联合芯片技术比较眼肌型重症肌无力(OMG)患者(4例)、全身型重症肌无力(GMG)患者(4例)与正常对照者(2例)血浆外泌体miRNA表达谱,筛选出在血浆中表达差异的外泌体源性miRNA。结果:OMG组较正常对照组显著差异表达的血浆外泌体miRNA共有4个,分别为上调的hsa-miR-3667-5p和下调的hsa-miR-3182、hsa-miR-6843-3p、hsa-miR-1273f;GMG组较正常对照组显著差异表达的miRNA共有48个,其中下调者16个,下调最显著的为hsa-miR-516a-5p,上调者32个,上调最显著的为hsa-miR-1273f。OMG组中差异表达的4个miRNA,在GMG中均有一致的差异表达,两者可能存在共同的发病机制。结论:差异表达的血浆外泌体miRNA可能在MG疾病的发生机制中起作用,并有可能作为诊断MG的生物标志物。

Objective:To analyze the expression profile of plasma exosomes microRNA(miRNA)in patients with myasthenia gravis(MG),and search for potential biomarkers for diagnosis of myasthenia gravis.Methods:The expression profiles of plasma exosomes miRNA in patients with ocular myasthenia gravis(OMG)(4 cases),generalized myasthenia gravis(GMG)(4 cases)and normal controls(2 cases)were compared by deep sequencing combined with microarray technology,and exosome-derived microRNAs differentially expressed in plasma were screened.Results:There were 4 plasma exosomes miRNA expressed significantly differently in OMG group compared with normal control group,which were up-regulated hsa-miR-3667-5p and down-regulated hsa-miR-3182,hsa-miR-6843-3p and hsa-miR-1273f.There were 48 miRNAs differentially expressed in GMG group compared with the normal control group,of which 16 were down-regulated,hsa-miR-516a-5p was significantly down-regulated,32 were up-regulated,and hsa-miR-1273f was significantly up-regulated.The four miRNAs that were differentially expressed in OMG group all showed consistent differentially expressed in GMG,and they may share the same pathogenesis.Conclusion:Differentially expressed plasma exosomes miRNA may play a role in the pathogenesis of MG diseases and may be used as biomarkers for the diagnosis of MG.