Roles of microRNAs in thalassemia: Mechanisms, biomarkers, and therapeutic implications – a narrative review

Abstract

Thalassemia, a kind of hemoglobin disorder, affects more than 1.5% of people worldwide. Small RNA molecules, known as microRNAs (miRNAs), are factors in controlling gene production, including hemoglobin production and disease development. This comprehensive review delves into the functions of miRNAs in the pathophysiology of thalassemia. The miRNAs miR-16 and miR-222 have been found to influence the dysregulation of erythropoiesis. These miRNAs act in impeding normal erythropoiesis, resulting in inefficient red blood cell (RBC) production and the premature demise of erythroid progenitor cells. Moreover, other miRNAs like miR-150, miR-210, and miR-485-3p regulate iron levels by pointing molecules such as transferrin receptor 1 (TfR1), ferritin, and hepcidin, which can worsen iron overload issues. Additionally, certain miRNAs have been recognized as markers for the identification of complications related to transfusions in individuals with thalassemia. The miRNAs like miR-451a, miR-20a, and miR-21 are associated with conditions such as iron overload and liver damage. Strategies involving the manipulation of the RNA molecules through mimics or inhibitors show promise in rebalancing gene activity and alleviating symptoms associated with thalassemia based on clinical trials conducted previously. The current review sheds light on how these miRNAs play a key role in modulating immune responses, and stress levels, along with organ-specific issues like heart or liver problems in patients with thalassemia. The miRNAs, including those mentioned above, impact immune cell performance, inflammation processes, and fibrosis development, contributing to the emergence of complications following transfusions. In conclusion, this comprehensive narrative review underlines the critical role of miRNAs in the pathogenesis of thalassemia. The findings illuminate their multifaceted potential as diagnostic biomarkers, therapeutic capacities, and cornerstones for developing tailored medical approaches. By harnessing these insights, clinicians and researchers may revolutionize thalassemia management, significantly improving patients’ health outcomes and quality of life.

Keywords: Erythropoiesis, Gene therapy, microRNA, Thalassemia