MiRNAs-Mediated Regulation of Oxidative Stress Pathways in Diabetes Complications: Molecular Insights and Therapeutic Opportunities.

Persistent hyperglycemia and uncontrolled type 2 diabetes contribute significantly to diabetes- related mortality by causing multiorgan and systemic injuries, particularly in vital organs such as the heart and kidneys, leading to both microvascular and macrovascular complications. The auto-oxidation of glucose increases oxidative stress, which in turn affects gene modulation and immune responses through the activation of four major pathways: (1) the polyol pathway, (2) the protein kinase C (PKC) pathway, (3) the advanced glycation end-product-receptor for advanced glycation end-product (AGE-RAGE) pathway, and (4) the hexosamine pathway. Oxidative stress and microRNAs (miRNAs) are closely related. These small non-coding RNAs bind to the 3' untranslated regions (3' UTRs) of target mRNAs, leading to mRNA degradation and translational repression. Although numerous studies have identified microRNAs (miRNAs) as important regulators of oxidative stress and diabetic complications, the available evidence remains fragmented. Therefore, this review aims to discuss the roles of miRNAs in oxidative stress-activated pathways and in the generation and detoxification of reactive oxygen species. It also highlights the potential of miRNAs as novel therapeutic targets in type 2 diabetes mellitus and outlines the challenges associated with their clinical application.