Analysis of microRNA-199a-3p expression in CD4+ T cells of systemic lupus erythematosus

Abstract

Objectives: Accumulating evidence have suggested microRNAs (miRNAs) play important roles in the pathogenesis of systemic lupus erythematosus (SLE). Here we aimed to explore aberrant expression of miRNAs in CD4⁺ T cells from SLE patients and their potential function in SLE pathogenesis.

Methods: First, next-generation sequencing was performed on CD4⁺ T cells from four SLE patients and three healthy controls (HCs). Candidate miRNAs were then validated in CD4⁺ T cells from 97 patients with SLE, 16 patients with rheumatoid arthritis, and 12 HCs using qRT-PCR. Then the relationship between the candidate miRNA and clinical characteristics was analyzed. Bioinformatics analysis and validation of the target genes of the candidate miRNA were performed.

Results: A total of 66 upregulated miRNAs and 70 downregulated miRNAs were found between SLE and normal CD4⁺ T cells samples. miR-199a-3p was identified significant upregulation in the CD4⁺ T cells of lupus patients. High expression of miR-199a-3p was correlated with several clinical characteristics including low C3 level, positive anti-dsDNA antibody, high ESR level, active lupus nephritis, and active disease activity. When distinguishing active LN from non-LN or active lupus from stable lupus, the AUCs of miR-199a-3p were 0.68 and 0.70, respectively. And the expression of miR-199a-3p, involved in JAK-STAT signaling pathway, was negatively correlated with the STAM expression in CD4⁺ T cells of SLE.

Conclusion: Our study suggested a novel and promising role of miR-199a-3p in CD4⁺ T cells for SLE. Further studies are needed to precisely determine the function of miR-199a-3p in this disease. Key Points • Aberrant expression of miRNAs in CD4⁺ T cells and their potential function in SLE pathogenesis remained unclear. • miR-199a-3p in CD4+ T cells plays a novel role in the pathogenesis of SLE and serves as a potential target for SLE.

Keywords: Biomarker; CD4+ T cells; JAK-STAT signaling pathway; Systemic lupus erythematosus; microRNA.