Expression Analysis of microRNAs in Peripheral Blood Mononuclear Cells in Type 2 Diabetes

Abstract

MicroRNAs (miRNAs) are involved in the regulation of glucose metabolism and inflammatory processes associated with type 2 diabetes (T2D) and have potential as biomarkers and therapeutic targets. We analysed the expression of miR-155-5p, miR-141-3p, miR-15b-5p, miR-18a-5p, and miR-379-5p in peripheral blood mononuclear cells (PBMCs) from 79 patients with T2D and 88 non-diabetic controls. Differential expression analysis revealed significant downregulation of miR-15b-5p, miR-155-5p, and miR-18a-5p, and significant upregulation of miR-379-5p in T2D patients. Among the individual miRNAs, miR-15b-5p showed the highest ability to distinguish between T2D and controls (AUC = 0.82, 95% CI 0.76–0.89, p = 0.001). A model combining the four differentially expressed miRNAs (miR-155-5p, miR-15b-5p, miR-18a-5p, and miR-379-5p) with age, sex, and BMI had an AUC of 0.98, compared with 0.93 for age, sex, and BMI alone (p = 0.004, paired DeLong test); the optimism-corrected AUC was 0.97, although the bootstrap procedure did not account for optimism arising from miRNA selection. Functional enrichment analysis identified MAPK, Hippo, FoxO, insulin, AMPK and TGF-β signalling as consistently enriched across analyses based on experimentally supported and predicted miRNA targets.