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

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

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 in situ 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 (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 by miR-125a Conclusion: Hsa_circ_0012919 could be regarded as a biomarker for SLE and hsa_circ_0012919 was the competitive endogenous RNA (ceRNA) for miR-125a-3p.

Keywords: Biomarker; System lupus erythematous; hsa_circ_0012919; miR-125a-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD11a Antigen / genetics*
  • CD11a Antigen / immunology
  • CD11a Antigen / metabolism
  • CD27 Ligand / genetics*
  • CD27 Ligand / immunology
  • CD27 Ligand / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Case-Control Studies
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cells, Cultured
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / metabolism
  • DNA (Cytosine-5-)-Methyltransferase 1 / genetics
  • DNA (Cytosine-5-)-Methyltransferase 1 / metabolism
  • DNA Methylation*
  • Female
  • Gene Expression Profiling / methods
  • Gene Regulatory Networks
  • Genetic Markers
  • Humans
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Oligonucleotide Array Sequence Analysis
  • RNA / genetics*
  • RNA / metabolism
  • RNA, Circular
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • CCL5 protein, human
  • CD11a Antigen
  • CD27 Ligand
  • CD70 protein, human
  • Cell Cycle Proteins
  • Chemokine CCL5
  • Genetic Markers
  • KLF13 protein, human
  • Kruppel-Like Transcription Factors
  • MIRN125 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Repressor Proteins
  • RNA
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNMT1 protein, human