hsa_circ_0012919 的下调，作为的海绵体，导致系统性红斑狼疮患者 CD4 T 细胞中 CD11a 和 CD70 的 DNA 甲基化。

The down-regulation of hsa_circ_0012919, the sponge for , contributes to DNA methylation of CD11a and CD70 in CD4 T cells of systemic lupus erythematous.

机构信息

Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Wujin Road 85, Hongkou District, Shanghai 200080, China.

Department of Dermatology, Minhang Hospital, Fudan University, Xinsong Road 170, Minhang District, Shanghai 201199, China

出版信息

Clin Sci (Lond). 2018 Nov 2;132(21):2285-2298. doi: 10.1042/CS20180403. Print 2018 Nov 15.

DOI:10.1042/CS20180403

PMID:30237316

Abstract

BACKGROUND

Systemic lupus erythematous (SLE) is an autoimmune disease characterized by the production of autoantibodies directed against various autoantigens. But the expression profiles and functions of circular RNAs (circRNAs) in SLE are still scarce.

OBJECTIVES

To explore the roles of circRNA in SLE and its potential diagnostic potential in SLE.

METHODS

SLE patients and healthy control subjects were recruited. CD4 T cells were isolated, circRNA microarray analysis were used to screen for circRNA candidate in CD4 T cells. Expression of DNMT1, CD11a and CD70, and methylation level of CD11a and CD70 were detected after transfecting hsa_circ_0012919-targetted siRNA. The network analysis of hsa_circ_0012919 was used by bioinformatics. Luciferase reporter assay and fluorescence hybridization (FISH) assay were used for screening for which miRNAs could bind with hsa_circ_0012919.

RESULTS

Twelve circRNAs were up-regulated and two circRNAs were down-regulated in SLE patients group after circRNA microarray analysis. Hsa_circ_0012919 was further confirmed to be significantly different between healthy control and SLE patients (<0.05) and associated with SLE characters (<0.05). Down-regulation of hsa_circ_0012919 (i) increased the expression of DNMT1 and reduced the expression of CD70, CD11a, (ii) reversed the DNA hypomethylation of CD11a and CD70 in CD4 T cells of SLE, but it could be reversed by down-regulation of DNMT1. Hsa_circ_0012919 regulated KLF13 and RANTES by Conclusion: Hsa_circ_0012919 could be regarded as a biomarker for SLE and hsa_circ_0012919 was the competitive endogenous RNA (ceRNA) for .

摘要

背景

系统性红斑狼疮（SLE）是一种自身免疫性疾病，其特征是产生针对各种自身抗原的自身抗体。但是，SLE 中环状 RNA（circRNA）的表达谱和功能仍然很少。

目的

探讨 circRNA 在 SLE 中的作用及其在 SLE 中的潜在诊断潜力。

方法

招募 SLE 患者和健康对照者。分离 CD4 T 细胞，使用 circRNA 微阵列分析筛选 CD4 T 细胞中的 circRNA 候选物。转染 hsa_circ_0012919 靶向 siRNA 后，检测 DNMT1、CD11a 和 CD70 的表达和 CD11a 和 CD70 的甲基化水平。使用生物信息学进行 hsa_circ_0012919 的网络分析。荧光杂交（FISH）试验筛选与 hsa_circ_0012919 结合的 miRNAs。

结果

circRNA 微阵列分析显示，SLE 患者组有 12 个 circRNA 上调，2 个 circRNA 下调。hsa_circ_0012919 在健康对照组和 SLE 患者组之间进一步证实差异显著（<0.05），且与 SLE 特征相关（<0.05）。hsa_circ_0012919 的下调（i）增加了 DNMT1 的表达并降低了 CD70、CD11a 的表达，（ii）逆转了 SLE 患者 CD4 T 细胞中 CD11a 和 CD70 的 DNA 低甲基化，但可被 DNMT1 的下调逆转。hsa_circ_0012919 通过调控 KLF13 和 RANTES。