title: 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.
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.
authors.affiliation: Department of Physiology, University of Debrecen, Nagyerdei krt. 98. PO box 22, Debrecen, 4012, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Gaál
authors.affiliation: Institute of Pediatrics, University of Debrecen, Nagyerdei krt. 98. PO box 32, Debrecen, PO, 4012, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Oláh
authors.affiliation: Institute of Internal Medicine, University of Debrecen, Nagyerdei krt. 98. PO box 20, Debrecen, 4012, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Rejtő
authors.affiliation: 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.
authors.forename: Bálint László
authors.initials: BL
authors.lastname: Bálint
authors.affiliation: Department of Physiology, University of Debrecen, Nagyerdei krt. 98. PO box 22, Debrecen, 4012, Hungary. csl@edu.unideb.hu.
authors.forename: László
authors.initials: L
authors.lastname: Csernoch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044127:Epigenesis, Genetic / Q000235:genetics; D019337:Hematologic Neoplasms / Q000235:genetics*; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D000090243:Nucleophosmin; D012097:Repressor Proteins / Q000235:genetics; D037761:Sirtuins / Q000235:genetics; D058494:Walker-Warburg Syndrome / Q000235:genetics*; D055815:Young Adult
chemical_list: D035683:MicroRNAs; C000716967:NPM1 protein, human; D012097:Repressor Proteins; D000090243:Nucleophosmin; C516592:SIRT6 protein, human; D037761:Sirtuins; C400300:HDAC4 protein, human; D006655:Histone Deacetylases
keywords: Acute myeloid leukemia; Anti-oncomiR; Histone deacetylase; Warburg-effect; microRNA; oncomiR