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Expression Levels of Warburg-Effect Related microRNAs Correlate with each Other and that of Histone Deacetylase Enzymes in Adult Hematological Malignancies with Emphasis on Acute Myeloid Leukemia

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Pathology & Oncology Research

Abstract

Disruption of epigenetic regulation and characteristic metabolic alterations (known as the Warburg-effect) are well-known hallmarks of cancer. In our study we investigated the expression levels of microRNAs and histone deacetylase enzymes via RT-qPCR in bone marrow specimens of adult patients suffering from hematological malignancies (total cohort n = 40), especially acute myeloid leukemia (n = 27). The levels of the three examined Warburg-effect related microRNAs (miR-378*, miR-23b, miR-26a) positively correlated with each other and the oncogenic miR-155 and miR-125b, while negatively with the level of the tumorsuppressor miR-124. Significant relationships have been confirmed between the levels of SIRT6, HDAC4 and the microRNAs listed above. In NPM1-mutated AML (n = 6), the level of miR-125b was significantly lower than in the group of AML patients not carrying this mutation (n = 13) (p < 0.05). In M5 FAB type of AML (n = 5), the level of miR-124 was significantly higher compared to the M2 group (n = 7) (p < 0.05). In two cases of FAB M5 AML, the levels of SIRT6 and miR-26a increased during the first 4 weeks of treatment. In the total cohort, white blood cell count at the time of the diagnosis significantly correlated with the levels of HDAC4, SIRT6, miR-124 and miR-26a. Our results suggest that Warburg-effect related microRNAs may have important role in the pathogenesis of leukemia, and the potential oncogenic property of HDAC4 and SIRT6 cannot be excluded in hematological malignancies. Elevated level of miR-125b can contribute to adverse prognosis of AML without NPM1 mutation. The prevailment of the tumorsuppressor property of miR-124 may depend on the accompanying genetic alterations.

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Acknowledgements

The authors are grateful for all members of the Genomic Medicine and Bioinformatic Core Facility (Department of Biochemistry and Molecular Biology, University of Debrecen), especially Tamás Kerekes for useful technical advices, Dóra Bojcsuk for performing cluster analysis and Erzsébet Mátyás for managing the ordering process of the necessary primers.

Financial support of our work was partially provided by the European Union and the European Social Fund (TÁMOP-4.1.2. E-13/1/KONV-2013-0010). Balint L. Balint is a Szodoray fellow of the University of Debrecen Medical Faculty, and during the preparation of the manuscript was a Magyary Zoltan fellow supported by the TÁMOP 4.2.4. A/2-11-1-2012-0001 grant implemented through the New Hungary Development Plan co-financed by the European Social Fund and the European Regional Development Fund. His work was supported by an internal Research University grant of the University of Debrecen entitled “Dissecting the genetic and epigenetic components of gene expression regulation in the context of the 1000 genomes project”.

Author Contributions

Gaál Zs.: design research, experimental procedures, data analysis, writing the manuscript.

Oláh É.: design research, supervision of experimental procedures, correction of the manuscript.

Rejtő L.: collection of bone marrow specimens, correction of the manuscript.

Bálint BL.: providing laboratory background (Genomic Medicine and Bioinformatic Core Facility, Department of Biochemistry and Molecular Biology, University of Debrecen) and primers, design research, supervision of experimental procedures, correction of the manuscript.

Csernoch L.: design research, supervision of experimental procedures, correction of the manuscript.

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Authors and Affiliations

  1. Department of Physiology, University of Debrecen, Nagyerdei krt. 98. PO box 22, Debrecen, 4012, Hungary

    Zsuzsanna Gaál & László Csernoch

  2. Institute of Pediatrics, University of Debrecen, Nagyerdei krt. 98. PO box 32, Debrecen, PO, 4012, Hungary

    Éva Oláh

  3. Institute of Internal Medicine, University of Debrecen, Nagyerdei krt. 98. PO box 20, Debrecen, 4012, Hungary

    László Rejtő

  4. Department of Biochemistry and Molecular Biology, Genomic Medicine and Bioinformatic Core Facility, University of Debrecen, Nagyerdei krt. 98. PO box 6, Debrecen, H-4012, Hungary

    Bálint László Bálint

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  1. Zsuzsanna Gaál
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  2. Éva Oláh
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  4. Bálint László Bálint
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Correspondence to László Csernoch.

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TÁMOP-4.1.2. E-13/1/KONV-2013-0010, TÁMOP 4.2.4. A/2–11–1-2012-0001

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Gaál, Z., Oláh, É., Rejtő, L. et al. Expression Levels of Warburg-Effect Related microRNAs Correlate with each Other and that of Histone Deacetylase Enzymes in Adult Hematological Malignancies with Emphasis on Acute Myeloid Leukemia. Pathol. Oncol. Res. 23, 207–216 (2017). https://doi.org/10.1007/s12253-016-0151-9

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  • DOI: https://doi.org/10.1007/s12253-016-0151-9

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