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.

Gaál, Zsuzsanna; Oláh, Éva; Rejto, László; Bálint, Bálint László; Csernoch, László

Gaál, Zsuzsanna; Oláh, Éva; Rejto, László; Bálint, Bálint László; Csernoch, László.

Afiliación

Gaál Z; Department of Physiology, University of Debrecen, Nagyerdei krt. 98. PO box 22, Debrecen, 4012, Hungary.
Oláh É; Institute of Pediatrics, University of Debrecen, Nagyerdei krt. 98. PO box 32, Debrecen, PO, 4012, Hungary.
Rejto L; Institute of Internal Medicine, University of Debrecen, Nagyerdei krt. 98. PO box 20, Debrecen, 4012, Hungary.
Bálint BL; 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.
Csernoch L; Department of Physiology, University of Debrecen, Nagyerdei krt. 98. PO box 22, Debrecen, 4012, Hungary. csl@edu.unideb.hu.

Pathol Oncol Res ; 23(1): 207-216, 2017 Jan.

Article en En | MEDLINE | ID: mdl-27864740

RESUMEN

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.

Asunto(s)

Neoplasias Hematológicas/genética; Histona Desacetilasas/genética; Leucemia Mieloide Aguda/genética; MicroARNs/genética; Síndrome de Walker-Warburg/genética; Adulto; Anciano; Anciano de 80 o más Años; Epigénesis Genética/genética; Humanos; Persona de Mediana Edad; Mutación/genética; Nucleofosmina; Proteínas Represoras/genética; Sirtuinas/genética; Adulto Joven

Palabras clave

Acute myeloid leukemia; Anti-oncomiR; Histone deacetylase; Warburg-effect; microRNA; oncomiR

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Neoplasias Hematológicas / MicroARNs / Síndrome de Walker-Warburg / Histona Desacetilasas Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Aged80 / Humans / Middle aged Idioma: En Revista: Pathol Oncol Res Asunto de la revista: NEOPLASIAS / PATOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Hungria Pais de publicación: Suiza

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