遗传学研究发现的自身免疫病的绝大部分易感位点位于基因组非编码区域。目前探索这些位点在疾病发生发展中的作用是这个领域的研究热点。本课题组前期发现了miRNA介导疾病遗传易感位点参与狼疮关键致病通路激活的机制。在此基础上，我们原创性研究环状RNA参与狼疮炎症损伤的作用机制，初步发现狼疮患者中高表达的circTNPO3参与了IL-6等炎症因子的表达调控。本项目基于前期研究基础提出以下假说：在狼疮患者中，功能性的SNP通过转录因子GATA-1来促进circTNPO3的产生，circTNPO3可以通过影响miRNA（或RNA结合蛋白）的功能参与炎症通路的过度激活从而参与疾病的发生发展。本项目拟通过功能获得和功能缺失策略，结合转录调控、信号传导和分子相互作用研究来解析circTNPO3介导遗传易感位点参与疾病发生发展的作用机制。该项目的预期成果将有助于理解SLE的发病机制，为疾病的个体化诊疗打下基础。

Most disease-associated SNPs of autoimmune diseases identified by GWAS are located in the noncoding regions of genome and now exploring the role of these SNPs in the development of autoimmune diseases is a hot area. Our previous work has found the mechanism that miRNA-mediated susceptible SNP involved in the pathogenesis of lupus. In this project, we originally studied the role of circular RNA in the pathogenesis of inflammatory injury in lupus, and preliminary findings show that circTNPO3, located in lupus susceptible region, is highly expressed in lupus patients, thus involving in the regulation of inflammatory factors expression such as IL-6. So we propose a hypothesis that in lupus patients, functional SNPs affect the expression of circTNPO3 by influencing the binding of transcription factor GATA1; further, circTNPO3 regulates the function of miRNA or RNA binding protein and participates in the development of the disease. This project aims to elucidate the role of circTNPO3 mediating the development of the disease by interaction with susceptible SNPs. And we will apply strategies, such as gain-of-function and loss-of-function, knock-out, transcriptional regulation, molecular interactions and so on, to investigate the mechanisms. The expected results of this project will help to understand the pathogenesis of SLE and lay the foundation for individualized diagnosis and treatment of the disease.