The miR-200 family in type 2 diabetes: therapeutic and biomarker perspectives

MicroRNAs (miRNAs) are critical regulators of gene expression and have emerged as promising biomarkers and therapeutic targets in type 2 diabetes (T2D). Among them, the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141, and miR-429) plays key roles in insulin sensitivity, pancreatic β-cell survival, and inflammation. Dysregulation of miR-200a/b and miR-200c has been linked to insulin resistance and β-cell apoptosis, although findings are context dependent, with miR-200c showing both protective and deleterious effects. Therapeutic approaches include the use of antagomiRs to inhibit miR-200a/b (to improve insulin sensitivity) and miR-200c mimics at physiological/ moderate level (to enhance β-cell resilience under oxidative stress). Advances in nanoparticle delivery systems (liposomes, micelles, dendrimers) and chemical modifications such as 2'-O-methyl, 2'-O-methoxyethyl, and locked nucleic acids have improved stability and efficacy, though barriers remain in achieving tissue specificity and minimizing immune activation. In addition to therapy, miR-200 family members are attractive non-invasive biomarkers, with recent studies reporting encouraging sensitivity and specificity for early T2D detection and monitoring of disease progression. However, major challenges persist, including delivery barriers, long-term safety concerns, and limited validation in large, multi-ethnic human cohorts. This review synthesizes current evidence on the dual potential therapeutic strategies of miR-200 inhibition and mimicry, evaluates their biomarker utility, and highlights future directions needed to overcome translational gaps. By addressing these limitations, miR-200-based strategies hold potential to advance toward clinical application in T2D.