Decreased microRNA(miR)-145 and increased miR-224 expression in T cells from patients with systemic lupus erythematosus involved in lupus immunopathogenesis

Abstract

SummarySystemic lupus erythematosus (SLE) is a systemic autoimmune disease with abnormal T cell immune responses. We hypothesized that aberrant expression of microRNAs (miRNAs) in T cells may contribute to the pathogenesis of SLE. First, we analysed the expression profiles of 270 human miRNAs in T cells from five SLE patients and five healthy controls and then validated those potentially aberrant-expressed miRNAs using real-time polymerase chain reaction (PCR). Then, the expression of mRNAs regulated by these aberrantexpressed miRNAs was detected using real-time PCR. Finally, miRNA transfection into Jurkat T cells was conducted for confirming further the biological functions of these miRNAs. The initial analysis indicated that seven miRNAs, including miR-145, miR-224, miR-513-5p, miR-150, miR516a-5p, miR-483-5p and miR-629, were found to be potentially abnormally expressed in SLE T cells. After validation, under-expressed miR-145 and over-expressed miR-224 were noted. We further found that STAT1 mRNA targeted by miR-145 was over-expressed and apoptosis inhibitory protein 5 (API5) mRNA targeted by miR-224 was under-expressed in SLE T cells. Transfection of Jurkat cells with miR-145 suppressed STAT1 and miR-224 transfection suppressed API5 protein expression. Over-expression of miR-224 facilitates activation-induced cell death in Jurkat cells. In the clinical setting, the increased transcript levels of STAT1 were associated significantly with lupus nephritis. In conclusion, we first demonstrated that miR-145 and miR-224 were expressed aberrantly in SLE T cells that modulated the protein expression of their target genes, STAT1 and API5, respectively. These miRNA aberrations accelerated T cell activation-induced cell death by suppressing API5 expression and associated with lupus nephritis by enhancing signal transducer and activator of transcription-1 (STAT)-1 expression in patients with SLE.

A plasma microRNA signature as a biomarker for acquired aplastic anemia

“…In our recent work, we identified concurrent downregulation of 4 miRNAs (miR-126-3p, miR-145-5p, miR-199a-5p, and miR-223-3p) in both CD4 + and CD8 + T cells from AA patients, 14 but dysregulation of the 4 miRNAs was not observed in AA plasma samples in the study herein. Previous reports in autoimmune diseases 12,20,[52][53][54][55][56][57][58][59] and cancers, [60][61][62][63] have also demonstrated discrepancies of expression profiles between cellular and circulating miRNAs. Systemic lupus erythematosus (SLE) patients exhibit distinct miRNA expression profiles in T cells [52][53][54][55] and plasma, 56 and miRNA profiles in T cells 12,57,58 and plasma 20,59 are inconsistent in MS.…”

Identification of novel microRNA signatures linked to acquired aplastic anemia

“…For example, decreased expression of miR-145-5p was detected in T cells from patients with myasthenia gravis 46 and systemic lupus erythematosus. 47 MiR-223-3p is overexpressed in T cells from patients with rheumatoid arthritis, 48 indicating the similarity and difference of miRNA expression in different type of diseases.…”

Post-Transcriptional Gene Regulation Makes Things Clearer in Renal Fibrosis

“…Altered expression of miRNAs in T lymphocytes from SLE patients accelerated T cell activationinduced cell death contributing to the pathogenesis of the disease. 10 Four miRNAs, which target genes involved in TGF-b signaling, were detected in plasma of SLE patients that distinguished SLE from other immune-mediated diseases, 11 but the significance of such results is quite uncertain considering the undefined cellular source of circulating miRNAs. Differentially expressed miRNAs were also found in kidney biopsies from lupus nephritis (LN) patients, although available studies did not describe any possible role or targets for the selected miRNAs.…”