Circulating miRNAs and tissue iron overload in transfusion-dependent β-thalassemia major: novel predictors and follow-up guide

Abstract

Tissue iron overload is a life-threatening scenario in children with transfusion-dependent β-thalassemia major, miRNAs that are involved in iron hemostasis could serve as therapeutic targets for control of iron overload. We aimed to find out the association between three iron-related miRNAs “miR-let-7d, miR-122, and miR-200b” and excess iron in tissues, in transfusion-dependent β-thalassemia major patients. Circulating miRNA expressions are measured in peripheral blood (PB) samples using qPCR of transfusion-dependent (TDT) β-thalassemia patients (n = 140) and normalized to non-transfusion-dependent (NTDT) β-thalassemia (n = 45). Results revealed that plasma expression levels of miR-let-7d and miR-200b were significantly downregulated in TDT patients; however, miR-122 was upregulated. In terms of tissue iron load, aberrant expression of miRNAs was significantly associated with increased—iron accumulation in hepatic and cardiac tissues. We concluded that circulating miRNAs are strong candidates that associate iron hemostasis in transfusion-dependent β-thalassemia major patients. And by extension, targeting miR-let-7d, miR-122, and miR-200 might serve as novel sensitive, specific and non-invasive predictor biomarkers for cellular damage under condition of tissue iron excess.