title: Decreased miR-146 expression in peripheral blood mononuclear cells is correlated with ongoing islet autoimmunity in type 1 diabetes patients 1miR-146.
abstract: BACKGROUND
  Type 1 diabetes mellitus (T1D) is a common autoimmune disease mediated by autoimmune attack against pancreatic β-cells. It has been reported that dysregulation of microRNAs (miRNAs) may contribute to the pathogenesis of autoimmune diseases, including T1D. The aim of the present study was to identify pathogenic miRNAs in peripheral blood mononuclear cells (PBMC) of T1D patients.
  
  
  METHODS
  Global miRNA and mRNA expression was profiled in PBMC from 12 patients with newly diagnosed T1D and 10 normal controls. Differently expressed miRNAs were validated in an independent set of patients and controls. The dynamic changes in miRNA and target gene expression were analyzed in T1D patients treated with either a short (6 months) or long (12-24 months) course of insulin. The association between miRNA expression and serum glutamic acid decarboxylase antibody (GADA) titers was also investigated.
  
  
  RESULTS
  Compared with normal controls, there were 26 miRNAs and 1218 genes differently expressed in PBMC of patients with newly diagnosed T1D. The greatest downregulation was for miR-146a (48% decrease; P < 0.05). Expression of its target genes, predicted to be tumor necrosis factor receptor-associated factor 6 (TRAF6), B cell CLL/lymphoma 11A (BCL11A), syntaxin 3 (STX3) and numb homolog (NUMB), was upregulated. Moreover, T1D patients on long-course insulin and optimized glucose control had sustained low expression of miR-146. Interestingly, decreased miR-146a expression was significantly associated with high serum GADA titers (P < 0.05).
  
  
  CONCLUSIONS
  The results suggest that dysregulation of miR-146 expression in PBMC may be associated with the ongoing autoimmune imbalance in T1D patients.
authors.affiliation: Department of Endocrine and Metabolic Diseases, Ruijin Hospital, School of Medicine, Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Minglan
authors.initials: M
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Ye
authors.forename: Bokai
authors.initials: B
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.forename: Ruixin
authors.initials: R
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Hong
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wang
authors.forename: Weiqiong
authors.initials: W
authors.lastname: Gu
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D015415:Biomarkers; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: miR-146; peripheral blood mononuclear cells; type 1 diabetes mellitus; 关键词：miR-146, 外周血单个核细胞，1型糖尿病