Hsa_circ_0012919 regulates expression of MDA5 by miR-125a-3p in CD4+ T cells of systemic lupus erythematous

Lupus. 2020 Jun;29(7):727-734. doi: 10.1177/0961203320920706. Epub 2020 Apr 22.

Abstract

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 (p < 0.05), methylation level of MDA5 promoter was significantly lower in CD4+ T cells of SLE patients (p < 0.05), and expression of MDA5 mRNA was correlated with SLE parameters (p < 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.

Keywords: Hsa_circ_0012919; MDA5; Systemic lupus erythematous; miR-125a-3p.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Case-Control Studies
  • DNA Methylation*
  • Down-Regulation
  • Female
  • Gene Expression Profiling
  • Humans
  • Interferon-Induced Helicase, IFIH1 / genetics*
  • Interferon-Induced Helicase, IFIH1 / metabolism
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / metabolism
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Promoter Regions, Genetic
  • RNA, Circular / genetics*
  • RNA, Messenger / metabolism

Substances

  • MIRN125 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA, Messenger
  • IFIH1 protein, human
  • Interferon-Induced Helicase, IFIH1