Aim: Autoimmune diabetes mellitus (defined as ADM) comprises classical type 1 diabetes mellitus (T1DM) and latent autoimmune diabetes in adults (LADA). In this study, microRNAs (miRNAs) expression profiles and functions in peripheral blood mononuclear cells (PBMCs) of ADM patients were mapped and used to explore epigenetic regulation of the pathogenesis of ADM.
Methods: PBMCs samples from T1DM patients, LADA patients, and type 2 diabetes mellitus (T2DM) patients, as well as age- and sex-matched healthy controls for T1DM and T2DM, respectively, were collected and were sequenced to screen the miRNAs expression profiles. The target genes were verified by dual-luciferase reporter assay. Silencing or overexpressing of the differentially expressed miRNAs, or simultaneously silencing the miRNAs and it's target gene, and then levels of the mRNAs, protein and cytokines were detected.
Results: miR-143-3p expression was upregulated in ADM patients. The target gene of miR-143-3p was identified as Fos-related antigen 2 (FOSL2). Transfection of a miR-143-3p inhibitor into PBMCs upregulated FOSL2 expression, resulting in a downregulated expression of the IL-2, TNF-α, and IFN-γ, and an upregulated expression of IL-6. Transfection of a miR-143-3p mimic into PBMCs downregulated FOSL2 expression, leading to an upregulation of IL-2 and TNF-α expression and a downregulation of IL-6 expression. When silencing FOSL2 while inhibiting miR-143-3p in PBMCs, there was no significant change in expression of the FOSL2 mRNA, protein and cytokines.
Conclusion: The expression of miR-143-3p in PBMCs from ADM patients is upregulated. miR-143-3p could function in the pathogenesis of ADM by modulating the inflammatory reaction through FOSL2.
Keywords: Autoimmune diabetes mellitus; Cytokines; FOSL2; PBMCs; miR-143-3p.