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

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.

Non-Coding RNAs in CD4+ T Cells: New Insights Into the Pathogenesis of Systemic Lupus Erythematosus

“…It was reported that RANTES is involved in the development of SLE, and the transcriptional factor KLF13 regulates the expression of RANTES in activated T cells (100). Zhang et al (101) demonstrated that hsa_circ_0012919 is highly expressed in lupus CD4 + T cells and participates in regulating the expression of RANTES and KLF13 by serving as the miR-125a-3p sponge. Moreover, inhibiting hsa_circ_0012919 corrects the DNA hypomethylation of CD70 and CD11a in lupus CD4 + T cells by promoting DNMT1 activity (101).…”

“…Zhang et al (101) demonstrated that hsa_circ_0012919 is highly expressed in lupus CD4 + T cells and participates in regulating the expression of RANTES and KLF13 by serving as the miR-125a-3p sponge. Moreover, inhibiting hsa_circ_0012919 corrects the DNA hypomethylation of CD70 and CD11a in lupus CD4 + T cells by promoting DNMT1 activity (101). The AKT signaling is over-activated in CD4 + T cells from SLE patients (102)(103)(104).…”

Functional roles of circular RNAs during epithelial-to-mesenchymal transition

“…CircRNAs have been identified as a determinant factor in many human diseases, including cardiovascular system diseases, neurological disorders, and cancer. Moreover, several studies have demonstrated that circRNAs can serve as prognostic biomarkers because of their characteristics [9][10][11][12][13].…”

The emerging landscape of circular RNAs in immunity: breakthroughs and challenges

“…Zhang C et al isolated CD4 + T cells where circRNA microarray study was conducted for screening out circRNA candidates. As indicated from the results, circ_0012919 reduction enriched the expression of DNMT1, decreased the expressions of CD70 and CD11a, and reversed the DNA hypomethylation of CD11a and CD70 in CD4 + T cells of systemic lupus erythematosus (SLE); however, it was reversible by DNMT1 reduction [51]. Circ_0005519 was reported to be upregulated and negatively related to hsa-let-7a-5p expression in CD4 + T cells of asthmatic cases.…”