Decreased micro RNA( miR)-145 and increased mi R-224 expression in T cells from patients with systemic lupus erythematosus involved in lupus immunopathogenesis.

Systemic lupus erythematosus ( SLE) is a systemic autoimmune disease with abnormal T cell immune responses. We hypothesized that aberrant expression of micro RNAs ( miRNAs) in T cells may contribute to the pathogenesis of SLE. First, we analysed the expression profiles of 270 human mi RNAs in T cells from five SLE patients and five healthy controls and then validated those potentially aberrant-expressed mi RNAs using real-time polymerase chain reaction ( PCR). Then, the expression of m RNAs regulated by these aberrant-expressed mi RNAs was detected using real-time PCR. Finally, mi RNA transfection into Jurkat T cells was conducted for confirming further the biological functions of these mi RNAs. The initial analysis indicated that seven mi RNAs, including mi R-145, mi R-224, mi R-513-5p, mi R-150, mi R-516a-5p, miR-483-5p and mi R-629, were found to be potentially abnormally expressed in SLE T cells. After validation, under-expressed mi R-145 and over-expressed mi R-224 were noted. We further found that STAT1 m RNA targeted by mi R-145 was over-expressed and apoptosis inhibitory protein 5 ( API5) m RNA targeted by mi R-224 was under-expressed in SLE T cells. Transfection of Jurkat cells with mi R-145 suppressed STAT1 and mi R-224 transfection suppressed API5 protein expression. Over-expression of mi R-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 mi R-145 and mi R-224 were expressed aberrantly in SLE T cells that modulated the protein expression of their target genes, STAT1 and API5, respectively. These mi RNA 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. [ABSTRACT FROM AUTHOR]