Upregulation of miR-214 Mediates Oxidative Stress in Hb H Disease via Targeting of ATF4

Thalassemia is a genetic disorder, occurring because of an imbalance in the globin chain production. Oxidative stress in erythroid cells of thalassemia is mainly generated from excess globin chains, by Fenton reaction, leading to hemolysis and ineffective erythropoiesis. Previously, data has shown that microRNAs (miRNAs) are involved in oxidative stress regulation in red blood cells (RBCs). microR-214 has been reported to respond with an external oxidative stress in erythroid cells by modulating activating transcription factor 4 (ATF4). In this study, we illustrated the expressions of miR-214 and ATF4 in Hb H (β4) disease, and Hb E (HBB: c.79G>A)/β-thalassemia (β-thal) reticulocyte samples. Our results showed miR-214 expression was increased in Hb H disease, but not significantly different in Hb E/β-thal reticulocytes. The ATF4 target was decreased in both thalassemic groups. Moreover, miR-214 expression level positively correlated with the reactive oxygen species (ROS) level, while it was negatively correlated with mean corpuscular volume (MCV), mean corpuscular hemoglobin (Hb) (MCH) and mean corpuscular Hb concentration (MCHC). We suggested that the upregulation of miR-214 correlated with the oxidative stress as well as anemia severity of Hb H disease patients, by suppression of ATF4. Understanding the oxidative pathways in erythrocyte could be useful to manage and relieve the clinical manifestation, such as anemia, in thalassemic patients.