CircRNA_100226/miR-875-3p/Ets-1轴调控B细胞分化在SLE发病中的作用机制及临床价值研究

B细胞异常分化在SLE发病中扮演重要角色。前期实验发现circRNA_100226在SLE患者血浆、PBMCs及B细胞中均表达降低。生物信息学分析发现circRNA_100226具有miR-875-3p结合位点，miR-875-3p对应靶基因为Ets-1。Ets-1是SLE的易感基因，可负调控B细胞终末分化。且我们预实验发现circRNA_100226可特异结合miR-875-3p，miR-875-3p可靶向结合Ets-1。由此推测circRNA_100226可能通过竞争吸附miR-875-3p调控Ets-1表达进而影响B细胞分化，导致SLE发生。本项目拟通过过表达和干扰circRNA_100226和/或miR-875-3p，探讨circRNA_100226/miR-875-3p/Ets-1轴调控B细胞分化在SLE发病中的作用机制及临床价值，为SLE防治新靶点及分子标志物研究提供科学依据。

Abnormal differentiation of B cell plays an important role in the pathogenesis of SLE. Our previous studies found that the expression of circRNA_100226 was down-regulated in plasma, peripheral blood mononuclear cells and B cells of SLE patients compared to normal controls. Bioinformatics analysis showed that circRNA_100226 contained binding sites of miR-875-3p, Ets-1 was the target gene of miR-875-3p. Studies have revealed that Ets-1 was a susceptible gene of SLE, and it played a negative regulatory role in the terminal differentiation of B cells. We also found that circRNA_100226 can specifically bind with miR-875-3p, and miR-875-3p can target with Ets-1.Thus, we speculated that circRNA_100226 may act as a competitive endogenous RNA to regulate the expression of Ets-1 through sponging miR-875-3p in SLE, thereby affecting the function of B cells in SLE patients and promoting the differentiation of B cells. This project intends to explore the mechanism and clinical value of circRNA_100226 / miR-875-3p / Ets-1 axis to regulate B cell differentiation by overexpressing and interfering with circRNA_100226 and / or miR-875-3p. And the elucidation of this mechanism can provide a scientific basis for the research of biomarker and the new target for the prevention and treatment of SLE.