Relevance of Circulating microRNA, and their Association with Islet Cell Autoantibodies in Type 1 Diabetes Pathogenesis

Abstract

The role of microRNAs (miRNAs) in the pathogenesis and progression of type 1 diabetes (T1D) has been described, but data remain scarce and conflicting. To evaluate the potential biological involvement of miRNA expression in the immune response and beta cell function in T1D. We screened 10 serum miRNAs from 142 subjects divided into three groups: healthy individuals (control group; n = 52) and patients at different stages of T1D progression, from the initial immunological manifestation, presenting islet cell autoantibodies (AbP group; n = 39), to partial and severe beta cell damage in T1D (recent T1D group; n = 51). Three miRNAs (miR-200c-3p, miR-301a-3p, and miR-382-5p) were highly expressed in the AbP and/or recent T1D groups compared to the control group. Furthermore, in the AbP group, miR-301a-3p and miR-382-5p were positively correlated with insulin autoantibody levels and miR-382-5p was negatively correlated with C-peptide levels. In the recent T1D group, miR-200c-3p expression was positively correlated with IA-2A levels. Enrichment analysis of differentially expressed miRNAs showed their involvement in immune response, inflammatory pathways, proliferation/survival/apoptosis mechanisms, bacterial and viral infection, and insulin resistance. Our data indicated that miR-200c-3p, miR-301a-3p, and miR-382-5p might be involved in T1D pathogenesis. Proliferative, metabolic, and immune responses were main pathways associated with serum miRNA target genes.