LncRNA-GAS5靶向调控miR-221/PTPN3信号在SLE发生中的作用和分子机制研究

系统性红斑狼疮(SLE)是一种病因及发病机制尚未明了的常见自身免疫性疾病。长链非编码RNA-GAS5（LncRNA-GAS5）是新近发现的可能参与SLE发生的一种新基因。申项前期工作提示LncRNA-GAS5基因启动子区rs145204276多态性与SLE遗传易感性密切相关，但具体机制不明。GAS5与miR-221及靶蛋白PTPN3可能形成一种竞争性信号轴在SLE发生中起重要调控作用，然而GAS5基因变异是否干扰了miR-221与GAS5的结合、影响GAS5的基因表达及靶向调控PTPN3在SLE发病中起作用尚不清楚。本研究拟联合使用SNPs和插入/缺失两个遗传学标记，运用病例对照及功能实验探索GAS5基因遗传变异与SLE发病的关联，揭示GAS5靶向调控miR-221/PTPN3信号在SLE发生中的作用和分子机制，从而为SLE疾病的诊断和治疗提供重要的理论依据。

Systemic lupus erythematosus (SLE) is a common autoimmune disease, but its etiology and pathogenesis have not yet fully understood. The long chain non coding RNA gene-GAS5 (LncRNA-GAS5) gene is a novel gene which may be involved in SLE, but its mechanism involved in the incidence of SLE is not clear. In the previous study, we found that the rs145204276 polymorphism in the promoter region of LncRNA-GAS5 gene is closely related to the genetic susceptibility of SLE, but the specific mechanism is unknown. GAS5 and miR-221 and target protein PTPN3 may form a competitive signal axis that plays an important role in the regulation of SLE. However, whether GAS5 gene mutation interferes with the binding of miR-221 and GAS5, affecting GAS5 gene expression and targeted regulation. The role of PTPN3 in the pathogenesis of SLE is unclear. This study intends to use two genetic markers of SNPs and insertion/deletion, and use case-control and functional experiments to explore the association between genetic variation of GAS5 gene and the pathogenesis of SLE, and to reveal The role and molecular mechanism of LncRNA-GAS5 target regulating miR-221/PTPN3 signal in patient with SLE, and provide an important theoretical basis for the diagnosis and treatment of SLE.