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miR-144 regulates oxidative stress tolerance of thalassemic erythroid cell via targeting NRF2

Annals of Hematology volume 98, pages 2045–2052 (2019)Cite this article

Abstract

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.

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Acknowledgments

We thank the Department of Pathology, Faculty of Medicine, and the Department of Molecular Biotechnology and Bioinformatics, Faculty of Science, Prince of Songkla University.

Authorship

KS was the principal investigator and takes primary responsibility for contributed to apply for funding, the study design, performed the experiment, interpretation of the data, drafting, and editing of the manuscript. NS contributed to the study design and the editing of the manuscript. KP and MW were responsible for specimen collection and the editing of the manuscript. SS contributed to the perform experiment and the editing of the manuscript. SF contributed to the study design and the editing of the manuscript. The final version of the article to be published was read and approved by all authors.

Funding

This work was supported by a Thailand research fund grant (TRG5780103), the government budget of Prince of Songkla University (MET6201015S), and the Faculty of Medical Technology, Prince of Songkla University.

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Affiliations

  1. Faculty of Medical Technology, Prince of Songkla University, 15, Kanjanavanit Rd. Hat Yai, Songkhla, 90110, Thailand

    Kanitta Srinoun

  2. Section for Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 25/25, 270 Rama VI Rd., Ratchathewi, Bangkok, 10400, Thailand

    Nuankanya Sathirapongsasuti

  3. Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, 25/25, Putthamonthon Sai 4 Rd. Salaya, Putthamonthon, Nakron Pratom, 73170, Thailand

    Kittiphong Paiboonsukwong & Suthat Fucharoen

  4. Department of Pathology, Faculty of Medicine, Prince of Songkla University, 15, Kanjanavanit Rd. Hat Yai, Songkhla, 90110, Thailand

    Somporn Sretrirutchai

  5. Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, 15, Kanjanavanit Rd. Hat Yai, Songkhla, 90110, Thailand

    Malai Wongchanchailert

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  1. Kanitta Srinoun
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  2. Nuankanya Sathirapongsasuti
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  3. Kittiphong Paiboonsukwong
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  6. Suthat Fucharoen
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Correspondence to Kanitta Srinoun.

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Srinoun, K., Sathirapongsasuti, N., Paiboonsukwong, K. et al. miR-144 regulates oxidative stress tolerance of thalassemic erythroid cell via targeting NRF2. Ann Hematol 98, 2045–2052 (2019). https://doi.org/10.1007/s00277-019-03737-4

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  • DOI: https://doi.org/10.1007/s00277-019-03737-4

Keywords

  • miR-144
  • Oxidative stress
  • Thalassemia
  • Hemolysis