Santos Aritania S, Santos-Bezerra Daniele Pereira, Ferreira Ludmila Rodrigues Pinto, Bando Silvia Y, Alves Laís Isidoro, Cunha-Neto Edecio, da Silva Maria Elizabeth Rossi
Laboratorio de Carboidratos e Radioimunoensaios, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Department of Morphology, RNA Systems Biology Laboratory, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Arch Med Res. 2025 Feb;56(2):103114. doi: 10.1016/j.arcmed.2024.103114. Epub 2024 Nov 2.
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.
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.
目的/假设：微小RNA（miRNA）在1型糖尿病（T1D）发病机制和进展中的作用已有描述，但数据仍然稀少且相互矛盾。
评估miRNA表达在T1D免疫反应和β细胞功能中的潜在生物学参与情况。
我们从142名受试者中筛选了10种血清miRNA，这些受试者分为三组：健康个体（对照组；n = 52）以及处于T1D进展不同阶段的患者，从最初出现胰岛细胞自身抗体的免疫表现（抗体阳性组；n = 39）到T1D中部分和严重的β细胞损伤（近期T1D组；n = 51）。
与对照组相比，三种miRNA（miR - 200c - 3p、miR - 301a - 3p和miR - 382 - 5p）在抗体阳性组和/或近期T1D组中高表达。此外，在抗体阳性组中，miR - 301a - 3p和miR - 382 - 5p与胰岛素自身抗体水平呈正相关，miR - 382 - 5p与C肽水平呈负相关。在近期T1D组中，miR - 200c - 3p表达与IA - 2A水平呈正相关。差异表达miRNA的富集分析表明它们参与免疫反应、炎症途径、增殖/存活/凋亡机制、细菌和病毒感染以及胰岛素抵抗。
我们的数据表明，miR - 200c - 3p、miR - 301a - 3p和miR - 382 - 5p可能参与T1D发病机制。增殖、代谢和免疫反应是与血清miRNA靶基因相关的主要途径。
