Unit of Paediatric Endocrinology and Metabolism, Unit of Diabetes Mellitus of Children and Adolescents, 2nd Department of Paediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece.
2nd Department of Obstetrics and Gynaecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Ippokratio General Hospital, 54642 Thessaloniki, Greece.
Int J Mol Sci. 2021 Nov 10;22(22):12165. doi: 10.3390/ijms222212165.
Type-1 diabetes mellitus (T1DM) is one of the most well-defined and complex metabolic disorders, characterized by hyperglycemia, with a constantly increasing incidence in children and adolescents. While current knowledge regarding the molecules related to the pathogenesis and diagnosis of T1DM is vast, the discovery of new molecules, such as micro ribonucleic acids (micro-RNAs, miRNAs), as well as their interactions with T1DM, has spurred novel prospects in the diagnosis of the disease. This review aims at summarizing current knowledge regarding miRNAs' biosynthesis and action pathways and their role as gene expression regulators in T1DM. MiRNAs follow a complex biosynthesis pathway, including cleaving and transport from nucleus to cytoplasm. After assembly of their final form, they inhibit translation or cause messenger RNA (mRNA) degradation, resulting in the obstruction of protein synthesis. Many studies have reported miRNA involvement in T1DM pathogenesis, mainly through interference with pancreatic b-cell function, insulin production and secretion. They are also found to contribute to β-cell destruction, as they aid in the production of autoreactive agents. Due to their elevated accumulation in various biological specimens, as well as their involvement in T1DM pathogenesis, their role as biomarkers in early preclinical T1DM diagnosis is widely hypothesized, with future studies concerning their diagnostic value deemed a necessity.
1 型糖尿病(T1DM)是一种最为明确和复杂的代谢紊乱疾病,其特征为高血糖,且在儿童和青少年中的发病率不断增加。虽然目前对于与 T1DM 的发病机制和诊断相关的分子有大量的了解,但新分子(如 micro ribonucleic acids miRNAs)的发现,以及它们与 T1DM 的相互作用,为该疾病的诊断带来了新的前景。
本篇综述旨在总结 miRNA 的生物合成和作用途径及其作为 T1DM 基因表达调节剂的作用的现有知识。miRNAs 遵循复杂的生物合成途径,包括从核到细胞质的切割和转运。在组装成最终形式后,它们抑制翻译或导致信使 RNA(mRNA)降解,从而阻止蛋白质合成。
许多研究报告了 miRNA 参与 T1DM 发病机制,主要通过干扰胰岛β细胞功能、胰岛素的产生和分泌。它们也有助于β细胞的破坏,因为它们有助于产生自身反应性物质。由于它们在各种生物样本中的大量积累,以及它们在 T1DM 发病机制中的参与,人们广泛假设它们可作为早期临床前 T1DM 诊断的生物标志物,未来的研究也认为有必要评估它们的诊断价值。