The down-regulation of hsa_circ_0012919, the sponge for miR-125a-3p, contributes to DNA methylation of CD11a and CD70 in CD4( ) T cells of systemic lupus erythematous
The down-regulation of hsa_circ_0012919, the sponge for miR-125a-3p, contributes to DNA methylation of CD11a and CD70 in CD4( ) T cells of systemic lupus erythematous
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miR-125a-3p 海绵 hsa_circ_0012919 的下调有助于系统性红斑狼疮 CD4( ) T 细胞中 CD11a 和 CD70 的 DNA 甲基化
DOI：
10.1042/cs20180403
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发表时间：
2018
期刊：
影响因子：
6
通讯作者：
Shi Weimin
中科院分区：
文献类型：
--
作者：
Zhang Chengzhong;Wang Xin;Chen Yue;Wu Zhouwei;Zhang Chao;Shi Weimin
系统性红斑狼疮（SLE）是一种自身免疫性疾病，其特征是产生针对多种自身抗原的自身抗体。目的探讨circRNA在系统性红斑狼疮（SLE）中的作用及其在SLE诊断中的应用价值。分离CD 4 +T细胞，利用circRNA微阵列分析筛选候选circRNA。检测靶向hsa_circ_0012919的siRNA转染后DNMT 1、CD 11 a和CD 70的表达及CD 11 a和CD 70的甲基化水平。利用生物信息学方法对hsa_circ_0012919进行网络分析。采用荧光素酶报告基因分析和荧光原位杂交（FISH）技术筛选与hsa_circ_0012919结合的miRNAs。结果circRNA芯片分析显示，SLE患者组中有12个circRNA表达上调，2个circRNA表达下调。进一步证实Hsa_circ_0012919在健康对照组和SLE患者组间差异有统计学意义（P<0.05），并与SLE的临床特征相关（P<0.05）。下调hsa_circ_0012919（i）增加SLE患者CD 4 + T细胞中DNMT 1的表达，降低CD 70、CD 11 a的表达;（ii）逆转SLE患者CD 4 +T细胞中CD 11 a和CD 70的DNA低甲基化，但DNMT 1的下调可逆转这种低甲基化。结论Hsa_circ_0012919可作为SLE的生物标志物，是miR-125 a-3 p的竞争性内源性RNA（ceRNA）。
BackgroundSystemic 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.ObjectivesTo explore the roles of circRNA in SLE and its potential diagnostic potential in SLE.MethodsSLE 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 fluorescencein situhybridization (FISH) assay were used for screening for which miRNAs could bind with hsa_circ_0012919.ResultsTwelve 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 (P<0.05) and associated with SLE characters (P<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 bymiR-125a.ConclusionHsa_circ_0012919 could be regarded as a biomarker for SLE and hsa_circ_0012919 was the competitive endogenous RNA (ceRNA) formiR-125a-3p.