LncRNA NEAT1作为ceRNA调节IL6表达在儿童系统性红斑狼疮的作用及机制研究

Systemic lupus erythematosus (SLE) was a chronic, multi-system autoimmune disease. Long noncoding RNAs (lncRNA) have recently been identified to be tightly linked to diverse autoimmune disease. LncRNA work through multiple mechanisms, including competitive endogenous RNA mechanism, namely the LncRNA bond with microRNA competitively with mRNA .The present study reported that NEAT1 expression was abnormally increased in SLE patients. Silencing NEAT1 significantly reduced the expression of IL6, which was important cytokines. But the mechanism was not clear. We reported IL6 was target gene of miRNAlet7i. We found NEAT contains a potential binding site for miRNA-let-7i in its 3′untranslated region after searching miRNA target database. So We speculate that NEAT1 function as a competing endogenous RNA, and form a feedback loop with IL6 and miRNAlet7i. This study will provide new way for the diagnosis and treatment of SLE.

系统性红斑狼疮(SLE)是一种原发性弥漫性自身免疫性疾病，发病机制尚不完全清楚。长链非编码RNA(lncRNA)在免疫相关疾病中起到重要的作用。LncRNA有多重作用机制，其中一种为竞争性内源RNA（ceRNA）机制，即lncRNA与mRNA 竞争性结合miRNA。研究报道SLE患者中lncRNA NEAT1表达升高，其表达水平与IL6表达呈正相关，但其具体机制还需进一步探讨。我们前期报到IL6是 miRNA let7i的靶基因，且通过生物信息预测发现，NEAT1与miRNA let7i也存在特异性结合位点，提示NEAT1与miRNAlet7i能直接作用。因此我们推测在NEAT1可能通过ceRNA机制竞争性结合miRNA let7i，解除miRNAlet7i对IL6表达的抑制，进而参与SLE的发病过程。本研究将通过体内、体外试验证实NEAT1的作用机制，为SLE的诊治提供新的思路。

系统性红斑狼疮(SLE)是一种原发性弥漫性自身免疫性疾病，发病机制尚不完全清楚。非编码RNA(lncRNA、circRNA、miRNA等)在免疫相关疾病中起到重要的作用。本研究通过对系统性红斑狼疮患儿及健康患儿进行lncRNA、circRNA、mRNA进行芯片筛查，发现系统性红斑狼疮患儿存在差异表达的lncRNA、circRNA、mRNA。课题组对将circRNA、lncRNA表达情况与临床特点进行可相关分析，发现circRNA、lncRNA表达与疾病活动度及诊断有一定相关性，可用于疾病诊断及活动度监测的生物标志物。课题组对芯片结果进行了生物信息分析（包括共表达网络构建、GO分析、KEGG分析、ceRNA网络构建、靶基因预测等），有助于非编码RNA在系统性红斑狼疮中的作用机制研究。LncRNA有多重作用机制，其中一种为竞争性内源RNA（ceRNA）机制，即lncRNA与mRNA 竞争性结合miRNA。本研究中发现狼疮患儿lncRNA NEAT1表达明星升高，IL6表达升高，NEAT1与miRNA let7i存在特异性结合位点，研究报道SLE患者中lncRNA NEAT1表达水平与IL6表达呈正相关，IL6是 miRNA let7i的靶基因，因此NEAT1可能通过ceRNA机制竞争性结合miRNA let7i，进而参与SLE的发病过程。