重症肌无力胸腺风险lncRNA失调网络识别及其调控Wnt信号通路的机制研究

Myasthenia gravis (MG) is an autoimmune disease characterized by neuromuscular junctiontransmission dysfunction. The pathogenesis of thymus in MG is not clear.It’s a new view to expound the molecular pathogenesis of MG basing on the dysfunctional relationship of lncRNA-mRNA/miRNA-mRNA in thymus of MG patients,which is caused by abnormal lncRNAs and their target gene sites, and dysregulation pathways of Wnt signaling pathway.The differential expression of lncRNA, miRNA and mRNA in the thymus of MG patients are analyzed in this study.The thymus specific regulatiory relationship of lncRNA-miRNA and miRNA-mRNA are identified by the data base of miRcode、Tarbase,et al.The lncRNA-miRNA-mRNA regulatiory network are constructed by bioinformatics methods,basing on the relationship between lncRNA-miRNA and miRNA-mRNA,some of which were verified in previous studies.Then，identifying the Wnt signaling pathways their sub-pathways, which are regulated by risk lncRNA-miRNA-mRNA. Finally, biluciferase report is applied to verify their abnormal regulationships and the control network of lncRNA in MG.The purpose of this subject is to analyze the pathogenesis of MG in a systematic level, especially perfecting the mechanism of thymus gene expression in MG. This subject will provide a basis theory for molecular diagnosis method and personalized medicine for MG patients in the future.

重症肌无力(MG)是神经-肌肉接头传递功能障碍的自身免疫疾病，其胸腺相关发病机制尚不明确。以MG胸腺相关风险的lncRNA-mRNA/miRNA-mRNA失调关系为切入点阐述lncRNA与靶基因异常及其调控的Wnt信号通路所致MG发病的分子机制是一个全新视角。本研究对MG患者胸腺组织中lncRNA、miRNA及mRNA的表达水平进行差异表达分析，结合miRcode、Tarbase等数据库，明确MG胸腺特异性lncRNA-miRNA及miRNA-mRNA；同时整合既往研究中已验证的MG相关的miRNA-mRNA关系对，构建MG胸腺风险lncRNA-miRNA-mRNA调控网络，并识别其调控的Wnt信号通路及其子通路，最终应用双荧光素酶报告验证其异常调控关系及调控网络。本研究旨在从系统水平解析MG的发病机制，特别在胸腺基因表达层面完善MG的致病机理，为日后MG相关分子诊治和个体化治疗提供依据。

重症肌无力(MG)是神经-肌肉接头传递功能障碍的自身免疫疾病，其胸腺相关发病机制尚不明确。以MG胸腺相关风险的lncRNA-mRNA/miRNA-mRNA失调关系为切入点阐述lncRNA与靶基因异常及其调控的Wnt信号通路所致MG发病的分子机制是一个全新视角。本研究对MG患者胸腺组织中lncRNA、miRNA及mRNA的表达水平进行差异表达分析，结合miRcode、Tarbase等数据库，明确MG胸腺特异性lncRNA-miRNA及miRNA-mRNA；同时整合既往研究中已验证的MG相关的miRNAmRNA关系对，构建MG胸腺风险lncRNA-miRNA-mRNA调控网络，并识别其调控的Wnt信号通路及其子通路，最终应用双荧光素酶报告验证其异常调控关系及调控网络。本研究旨在从系统水平解析MG的发病机制，特别在胸腺基因表达层面完善MG的致病机理，为日后MG相关分子诊治和个体化治疗提供依据。