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

Aims/hypothesis: The role of microRNAs (miRNAs) in the pathogenesis and progression of type 1 diabetes (T1D) has been described, but data remain scarce and conflicting.

Objectives: To evaluate the potential biological involvement of miRNA expression in the immune response and beta cell function in T1D.

Methods: 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).

Results: 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.

Conclusion: 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.