系统性红斑狼疮患者CD4+T细胞miR-126及宿主基因EGFL7DNA甲基化状态分析

目的: 探讨系统性红斑狼疮(SLE)患者CD4⁺T细胞miR-126宿主基因EGFL7的甲基化水平对miR-126表达的调控。方法: 采用实时qPCR检测SLE患者CD4⁺T细胞miR-126及EGFL7 mRNA表达水平;亚硫酸氢钠基因组测序法检测EGFL7基因启动子区甲基化状态。结果: miR-126及其宿主基因EGFL7在SLE患者CD4⁺T细胞表达上调(P<0.01),EGFL7 mRNA表达水平与miR-126的表达呈正相关(r=0.538,P=0.015)。miR-126是一个内含子miRNA,位于宿主基因EGFL7基因座第7个内含子中,其自身的基因序列中包含29个CpG位点。但该区域甲基化水平在SLE患者CD4⁺T细胞和正常对照组间差异无统计学意义(P=0.907)。而SLE患者CD4⁺T细胞中EGFL7基因启动子区甲基化水平显著降低(P<0.05)。结论: SLE患者CD4⁺T细胞miR-126宿主基因EGFL7启动子区甲基化状态调控宿主基因本身及其miR-126的表达。

DNA methylation status of miR-126 and its host gene EGFL7 in CD4+T cells from patients with systemic lupus erythematosus

Objective: To explore the mechanisms by which DNA methylation regulates miR-126 and its host gene EGFL7 in CD4⁺T cells from patients with systemic lupus erythematosus(SLE). Methods: We analyzed the expression and the DNA methylation status within promoter region of EGFL7 and miR-126 by real-time qPCR and bisulfite genomic sequencing analysis. Results: miR-126 and EGFL7 mRNA expression was upregulated in CD4⁺T cells from SLE compared with that from healthy controls(P<0.01).EGFL7 mRNA level was positively correlated with miR-126 expression in CD4⁺T cells from SLE(r=0.538,P=0.015).The average methylation level of EGFL7 promoter in CD4⁺T cells from SLE was lower than that from healthy controls(P<0.05). Conclusion: The upregulation of miR-126 and its host gene EGFL7 expression in CD4⁺T cells from SLE is associated with the hypomethylation of the EGFL7 promoter.