Decreased miR-146 expression in peripheral blood mononuclear cells is correlated with ongoing islet autoimmunity in type 1 diabetes patients 1miR-146.

Abstract

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. 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. 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). The results suggest that dysregulation of miR-146 expression in PBMC may be associated with the ongoing autoimmune imbalance in T1D patients.