title: Decreased microRNA(miR)-145 and increased miR-224 expression in T cells from patients with systemic lupus erythematosus involved in lupus immunopathogenesis.
abstract: Systemic 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 aberrant-expressed 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, miR-516a-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.
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Buddhist Dalin Tzu Chi General Hospital, Chia-Yi, Taiwan.
authors.forename: M-C
authors.initials: MC
authors.lastname: Lu
authors.forename: N-S
authors.initials: NS
authors.lastname: Lai
authors.forename: H-C
authors.initials: HC
authors.lastname: Chen
authors.forename: H-C
authors.initials: HC
authors.lastname: Yu
authors.forename: K-Y
authors.initials: KY
authors.lastname: Huang
authors.forename: C-H
authors.initials: CH
authors.lastname: Tung
authors.forename: H-B
authors.initials: HB
authors.lastname: Huang
authors.forename: C-L
authors.initials: CL
authors.lastname: Yu
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D005260:Female; D006801:Humans; D019169:Jurkat Cells; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis; D050794:STAT1 Transcription Factor / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology*; D059467:Transcriptome; D014162:Transfection
chemical_list: C108386:API5 protein, human; D051017:Apoptosis Regulatory Proteins; C541010:MIRN145 microRNA, human; C546140:MIRN224 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human