中文摘要
已有研究表明微小RNA(miRNA)与系统性红斑狼疮(SLE)发病密切相关。T细胞内miRNA的表达及功能异常引起SLE患者T细胞的功能异常,导致疾病的发生、发展。新近研究发现环状RNA(circRNA)可吸附miRNA,影响其功能发挥。核内circRNA具备增强其编码基因转录、与经典线性剪接竞争等功能。据此,我们假设:T细胞circRNA异常可通过影响其吸附miRNA和调控基因转录等功能,造成T细胞功能异常,从而参与SLE发病。本课题拟收集SLE患者和正常对照T细胞和相关临床资料,借助circRNA芯片和荧光定量PCR技术,建立SLE及不同临床亚型患者T细胞circRNA的表达谱;针对SLE患者T细胞异常表达circRNA,运用生物信息学、慢病毒过表达和RNA干扰等技术,探讨其在SLE患者T细胞炎症细胞因子分泌等功能异常中的作用,初步揭示circRNA在SLE发病中可能的作用机制。
英文摘要
Previous studies have established the relevance of microRNA (miRNA) in the pathogenesis of systemic lupus erythematosus (SLE). Aberrant expression and function of miRNAs in T cells induce dysfunction of T cells and lead to the initiation and progression of SLE. Recent studies have shown that circular RNA (circRNA) can serve as miRNA sponge and thereby block the function of miRNA. CircRNA in nucleus can promote the transcription of its parental genes and compete with canonical splicing. Based on these evidences above, we hypothesize that aberrant expression of circRNA in T cells may affect its functions in sponging miRNA and regulating gene transcription, lead to dysfunction of T cells, and partake in the etiology of SLE. Therefore, we plan to collect circulating T cells and clinical data from SLE patients and healthy controls and then establish the expression profile of circRNA in T cells of SLE patients by virtue of microarray and Real-time PCR. As for the differentially expressed circRNA in SLE patients, we will utilize bioinformatics methods and perform overexpression and knockdown of circRNA, uncovering its role in T cell function such as cytokine secretion and the pathogenesis of SLE.
