新疆维吾尔族、汉族溃疡性结肠炎microRNA及mRNA的筛选及调控机制研究

Our earlier studies have shown differences in ulcerative colits (UC)between Uygur and Han patients : the onset age of UC in Uygur patient was lower than Han patients .The age distribution in Uygur patients was less widespread than Han patients .Comparing with Han patients,it showed the more severity, more complications,poorer treatment and higher recurrence rate in Uygur UC patients.Functionally relevant HLA-DRB1,FUT2 and IL-23R gene variants were associated with UC,suggesting that they played a potential role in the clinical heterogeneity of UC between Uygur and Han patients. By means of gene microarray ,we focus investigation on the altered expression of miRNAs and analyze the altered expression of miRNAs and mRNA in inactive and active UC between Uygur and Han patients.The miRNA microarray expression data is confirmed by performing RT-PCR.Both miRNA and gene expression profiles are integrated by correlation analysis to identify dysregulated miRNAs with their corresponding predicted target mRNA.Based on the latest studies, Bio-Function Analysis tool is used to filtering out the altered miRNA.To assess the relationship between the dysregulated miRNAs and stage ,treatment of UC,RT-PCR and western blot are applied to invest the expression of miRNA and target gene. In order to identify target mRNAs of miRNAs potentially play a role in UC pathogenesis, animal experiment will performed. The aim of the present study is to evaluate the role of aberrant miRNA expression in pathogenesis and treatment Of different nationnality UC patients.

我们前期研究发现，新疆地区维、汉两民族溃疡性结肠炎(UC)具有不同的特点：维族患者为单一发病年龄高峰且发病年龄小,病情重、病变广泛、并发症发生率高，药物治疗差且复发率高；同时明确了HLA-DRB1、FUT2和IL-23R基因多态性与UC发病存在民族差异性。本研究利用基因芯片探讨新疆维、汉两民族UC miRNA及mRNA的差异表达，分析不同民族活动期及缓解期UC miRNA表达情况，并应用荧光定量PCR对差异基因进行验证；建立miRNA及其靶基因调控网络，结合GO分类、Pathway分析及当前研究热点筛选本研究相关的差异miRNA,并对差异miRNA进行靶点预测；通过RT-PCR、Western blot分析相关差异miRNA及其靶基因与不同民族UC临床表型、治疗的相关性；利用UC动物模型验证差异miRNA在UC发生、发展过程中的调节作用。为研究不同民族UC的发病机制、治疗靶点提供依据。