Publication: miR-144 regulates oxidative stress tolerance of thalassemic erythroid cell via targeting NRF2
Issued Date
2019-09-01
Resource Type
ISSN
14320584
09395555
09395555
Other identifier(s)
2-s2.0-85068157013
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Annals of Hematology. Vol.98, No.9 (2019), 2045-2052
Suggested Citation
Kanitta Srinoun, Nuankanya Sathirapongsasuti, Kittiphong Paiboonsukwong, Somporn Sretrirutchai, Malai Wongchanchailert, Suthat Fucharoen miR-144 regulates oxidative stress tolerance of thalassemic erythroid cell via targeting NRF2. Annals of Hematology. Vol.98, No.9 (2019), 2045-2052. doi:10.1007/s00277-019-03737-4 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/51438
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
miR-144 regulates oxidative stress tolerance of thalassemic erythroid cell via targeting NRF2
Abstract
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. Thalassemia has a high prevalence in Thailand. Oxidative damage to erythroid cells is known to be one of the major etiologies in thalassemia pathophysiology. Oxidative stress status of thalassemia is potentiated by the heme, nonheme iron, and free iron resulting from imbalanced globin synthesis. In addition, levels of antioxidant proteins are reduced in α-thalassemia and β-thalassemia erythrocytes. However, the primary molecular mechanism for this phenotype remains unknown. Our study showed a high expression of miR-144 in β- and α-thalassemia. An increased miR-144 expression leads to decreased expression of nuclear factor erythroid 2-related factor 2 (NRF2) target, especially in α-thalassemia. In α-thalassemia, miR-144 and NRF2 target are associated with glutathione level and anemia severity. To study the effect of miR-144 expression, the gain-loss of miR-144 expression was performed by miR inhibitor and mimic transfection in the erythroblastic cell line. This study reveals that miR-144 expression was upregulated, whereas NRF2 expression and glutathione levels were decreased in comparison with the untreated condition after miR mimic transfection, while the reduction of miR-144 expression contributed to the increased NRF2 expression and glutathione level compared with the untreated condition after miR inhibitor transfection. Moreover, miR-144 overexpression leads to significantly increased sensitivity to oxidative stress at indicated concentrations of hydrogen peroxide (H2O2) and rescued by miR-144 inhibitor. Taken together, our findings suggest that dysregulation of miR-144 may play a role in the reduced ability of erythrocyte to deal with oxidative stress and increased RBC hemolysis susceptibility especially in thalassemia.