Department of Dermatology, Jiangsu Province Hospital, the First affiliated Hospital with Nanjing Medical University, China.
*These authors contributed equally to this work.
Lupus. 2020 Jun;29(7):727-734. doi: 10.1177/0961203320920706. Epub 2020 Apr 22.
Systemic lupus erythematous (SLE) is an autoimmune disease with production of various autoantibodies directed against various autoantigens. But the research on melanoma differentiation-associated gene 5 (MDA5) in SLE is still scarce. Here we try to elucidate the effect of hsa_circ_0012919 on MDA5 and its potential clinical value in SLE. CD4+ T cells from SLE patients and healthy control subjects were isolated. Expression of hsa_circ_0012919 and MDA5, and methylation level of MDA5 promoter were detected. Then expression and methylation level of MDA5 promoter was examined after transfection of hsa_circ_0012919-targeted siRNA and plasmids. Expression of hsa_circ_0012919 and MDA5 were further confirmed to be significantly higher in CD4+ T cells of SLE patients ( < 0.05), methylation level of MDA5 promoter was significantly lower in CD4+ T cells of SLE patients ( < 0.05), and expression of MDA5 mRNA was correlated with SLE parameters ( < 0.05). Downregulation or overexpression of hsa_circ_0012919 regulated (1) the expression of MDA5 in a dose-dependent manner and (2) the DNA methylation of MDA5 promoter in CD4+ T cells of SLE. Finally, hsa_circ_0012919 could regulate MDA5 by miR-125a-3p. Hsa_circ_0012919 regulated the expression and methylation of MDA5 in the CD4+ T cells of SLE patients, and hsa_circ_0012919 could regulate MDA5 by miR-125a-3p.
系统性红斑狼疮（SLE）是一种自身免疫性疾病，会产生针对各种自身抗原的各种自身抗体。但关于黑色素瘤分化相关基因 5（MDA5）在 SLE 中的研究仍很少。在这里，我们试图阐明 hsa_circ_0012919 对 MDA5 的影响及其在 SLE 中的潜在临床价值。从 SLE 患者和健康对照者中分离 CD4+T 细胞。检测 hsa_circ_0012919 和 MDA5 的表达以及 MDA5 启动子的甲基化水平。然后，转染 hsa_circ_0012919 靶向 siRNA 和质粒后，检测 MDA5 启动子的表达和甲基化水平。进一步证实，SLE 患者 CD4+T 细胞中 hsa_circ_0012919 和 MDA5 的表达明显升高（<0.05），SLE 患者 CD4+T 细胞中 MDA5 启动子的甲基化水平明显降低（<0.05），MDA5 mRNA 的表达与 SLE 参数相关（<0.05）。下调或过表达 hsa_circ_0012919 以剂量依赖的方式调节（1）CD4+T 细胞中 MDA5 的表达和（2）SLE 患者 CD4+T 细胞中 MDA5 启动子的 DNA 甲基化。最后，hsa_circ_0012919 可以通过 miR-125a-3p 调节 MDA5。hsa_circ_0012919 调节 SLE 患者 CD4+T 细胞中 MDA5 的表达和甲基化，hsa_circ_0012919 可以通过 miR-125a-3p 调节 MDA5。
