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Article

Epigenetic regulation of miRNA-124 and multiple downstream targets is associated with treatment response in myeloid malignancies

  • Authors:
    • Hongbin Liu
    • Phillip Pattie
    • Sahan Chandrasekara
    • Andrew Spencer
    • Anthony E. Dear
  • View Affiliations / Copyright

    Affiliations: Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria 3004, Australia, Department of Medicine, Eastern Health Clinical School, Monash University, Melbourne, Victoria 3128, Australia
  • Pages: 2175-2180
    |
    Published online on: July 25, 2016
       https://doi.org/10.3892/ol.2016.4912
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Abstract

Epigenetic regulation of microRNA (miRNA) expression has recently been implicated in the pathogenesis of myelodysplastic syndrome (MDS). Particular interest has focused on miRNA‑124 expression, which is inhibited in MDS and has recently been demonstrated to be upregulated in response to epigenetic treatment (EGT). Previous studies have determined the in vitro and in vivo expression of miRNA‑124 and several molecular targets, including cyclin‑dependent kinase (CDK) 4, CDK6 and enhancer of zeste homolog 2 (EZH2), in order to elucidate the molecular mechanisms associated with the miRNA‑124‑mediated therapeutic response to EGT in MDS and identify additional potential biomarkers of early EGT treatment response in myeloid malignancies. In vitro studies in the HL60 leukemic cell line identified upregulation of miRNA‑124 expression in response to single‑agent EGT with either azacytidine (AZA) or the histone deacetylase inhibitor panobinostat (LBH589). Combination EGT with AZA and LBH589 resulted in significant additive induction of miRNA‑124 expression. Expression of downstream targets of miRNA‑124, including CDK4, CDK6 and EZH2, in response to single agent and combined EGT was determined in HL60 cells. Single and combination EGT treatment resulted in inhibition of CDK4, CDK6 and EZH2 expression with combination EGT resulting in a significant and additive inhibitory effect. In vivo studies using peripheral blood mononuclear cells from patients receiving combination EGT for high risk MDS or acute myeloid leukemia demonstrated significant induction of miRNA‑124 and inhibition CDK4 and CDK6 messenger (m)RNA expression in patients that responded to combination EGT. A trend to inhibited EZH2 mRNA expression was also identified in response to combination EGT. Overall, the present observations identify a potential molecular mechanism for miRNA‑124‑mediated response to EGT involving regulation of CDK4, CDK6 and EZH2 expression. In addition, the present findings further qualify miRNA‑124 as a possible biomarker of early response to EGT in myeloid malignancies and potentially a valid therapeutic target, together with CDK4, CDK6 and EZH2.
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1 

Vasilatou D, Papageorgiou SG, Dimitriadis G and Pappa V: Epigenetic alterations and microRNAs: New players in the pathogenesis of myelodysplastic syndromes. Epigenetics. 8:561–570. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Tan PT and Wei AH: The epigenomics revolution in myelodysplasia: A clinico-pathological perspective. Pathology. 43:536–546. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, et al: Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: A randomised, open-label, phase III study. Lancet Oncol. 10:223–232. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Ornstein MC, Mukherjee S and Sekeres MA: More is better: Combination therapies for myelodysplastic syndromes. Best Pract Res Clin Haematol. 28:22–31. 2015. View Article : Google Scholar : PubMed/NCBI

5 

Chen CZ: MicroRNAs as oncogenes and tumor suppressors. N Engl J Med. 353:1768–1771. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Dickstein J, Senyuk V, Premanand K, Laricchia-Robbio L, Xu P, Cattaneo F, Fazzina R and Nucifora G: Methylation and silencing of miRNA-124 by EVI1 and self-renewal exhaustion of hematopoietic stem cells in murine myelodysplastic syndrome. Proc Natl Acad Sci USA. 107:9783–9788. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Xia Q, Hu J and Meng YS: Abnormal expression of microRNA-124 in patients with leukemia or myelodysplastic syndrome and its significance. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 20:358–361. 2012.PubMed/NCBI

8 

Castoro RJ, Dekmezian M, Saraf AJ, Watanabe Y, Chung W, Adhab SE, Jelinek J and Issa JP: MicroRNA 124 and its role in response to epigenetic therapy in patients with acute myelogenous leukemia and myelodysplastic syndrome. Blood. 112:5982008.

9 

Lujambio A, Ropero S, Ballestar E, Fraga MF, Cerrato C, Setién F, Casado S, Suarez-Gauthier A, Sanchez-Cespedes M, Git A, et al: Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res. 67:1424–1429. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Tan P, Wei A, Mithraprabhu S, Cummings N, Liu HB, Perugini M, Reed K, Avery S, Patil S, Walker P, et al: Dual epigenetic targeting with panobinostat and azacitidine in acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood Cancer J. 4:e1702014. View Article : Google Scholar : PubMed/NCBI

11 

Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, Pinto A, Beran M, de Witte TM, Stone RM, et al: Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 108:419–425. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2 (−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Liu HB, Mayes PA, Perlmutter P, McKendrick JJ and Dear AE: The anti-leukemic effect and molecular mechanisms of novel hydroxamate and benzamide histone deacetylase inhibitors with 5-aza-cytidine. Int J Oncol. 38:1421–1425. 2011.PubMed/NCBI

14 

Wong KY, So CC, Loong F, Chung LP, Lam WW, Liang R, Li GK, Jin DY and Chim CS: Epigenetic inactivation of the miR-124-1 in haematological malignancies. PLoS One. 6:e190272011. View Article : Google Scholar : PubMed/NCBI

15 

Agirre X, Vilas-Zornoza A, Jiménez-Velasco A, Martin-Subero JI, Cordeu L, Gárate L, San José-Eneriz E, Abizanda G, Rodríguez-Otero P, Fortes P, et al: Epigenetic silencing of the tumor suppressor microRNA Hsa-miR-124a regulates CDK6 expression and confers a poor prognosis in acute lymphoblastic leukemia. Cancer Res. 69:4443–4453. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Chen X, He D, Dong XD, Dong F, Wang J, Wang L, Tang J, Hu DN, Yan D and Tu L: MicroRNA-124a is epigenetically regulated and acts as a tumor suppressor by controlling multiple targets in uveal melanoma. Invest Ophthalmol Vis Sci. 54:2248–2256. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Chang CJ and Hung MC: The role of EZH2 in tumour progression. Br J Cancer. 106:243–247. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Sashida G, Harada H, Matsui H, Oshima M, Yui M, Harada Y, Tanaka S, Mochizuki-Kashio M, Wang C, Saraya A, et al: Ezh2 loss promotes development of myelodysplastic syndrome but attenuates its predisposition to leukaemic transformation. Nat Commun. 5:41772014. View Article : Google Scholar : PubMed/NCBI

19 

Herrera-Merchan A, Arranz L, Ligos JM, de Molina A, Dominguez O and Gonzalez S: Ectopic expression of the histone methyltransferase Ezh2 in haematopoietic stem cells causes myeloproliferative disease. Nat Commun. 3:6232012. View Article : Google Scholar : PubMed/NCBI

20 

Tanaka S, Miyagi S, Sashida G, Chiba T, Yuan J, Mochizuki-Kashio M, Suzuki Y, Sugano S, Nakaseko C, Yokote K, et al: Ezh2 augments leukemogenicity by reinforcing differentiation blockage in acute myeloid leukemia. Blood. 120:1107–1117. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Agarwal P, Alzrigat M, Párraga AA, Enroth S, Singh U, Ungerstedt J, Österborg A, Brown PJ, Ma A, Jin J, et al: Genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in multiple myeloma reveals the importance of Polycomb gene targeting and highlights EZH2 as a potential therapeutic target. Oncotarget. 7:6809–6823. 2016.PubMed/NCBI

22 

Bose P, Simmons GL and Grant S: Cyclin-dependent kinase inhibitor therapy for hematologic malignancies. Expert Opin Investig Drugs. 22:723–738. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Fandy TE, Herman JG, Kerns P, Jiemjit A, Sugar EA, Choi SH, Yang AS, Aucott T, Dauses T, Odchimar-Reissig R, et al: Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies. Blood. 114:2764–2773. 2009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Liu H, Pattie P, Chandrasekara S, Spencer A and Dear AE: Epigenetic regulation of miRNA-124 and multiple downstream targets is associated with treatment response in myeloid malignancies. Oncol Lett 12: 2175-2180, 2016.
APA
Liu, H., Pattie, P., Chandrasekara, S., Spencer, A., & Dear, A.E. (2016). Epigenetic regulation of miRNA-124 and multiple downstream targets is associated with treatment response in myeloid malignancies. Oncology Letters, 12, 2175-2180. https://doi.org/10.3892/ol.2016.4912
MLA
Liu, H., Pattie, P., Chandrasekara, S., Spencer, A., Dear, A. E."Epigenetic regulation of miRNA-124 and multiple downstream targets is associated with treatment response in myeloid malignancies". Oncology Letters 12.3 (2016): 2175-2180.
Chicago
Liu, H., Pattie, P., Chandrasekara, S., Spencer, A., Dear, A. E."Epigenetic regulation of miRNA-124 and multiple downstream targets is associated with treatment response in myeloid malignancies". Oncology Letters 12, no. 3 (2016): 2175-2180. https://doi.org/10.3892/ol.2016.4912
Copy and paste a formatted citation
x
Spandidos Publications style
Liu H, Pattie P, Chandrasekara S, Spencer A and Dear AE: Epigenetic regulation of miRNA-124 and multiple downstream targets is associated with treatment response in myeloid malignancies. Oncol Lett 12: 2175-2180, 2016.
APA
Liu, H., Pattie, P., Chandrasekara, S., Spencer, A., & Dear, A.E. (2016). Epigenetic regulation of miRNA-124 and multiple downstream targets is associated with treatment response in myeloid malignancies. Oncology Letters, 12, 2175-2180. https://doi.org/10.3892/ol.2016.4912
MLA
Liu, H., Pattie, P., Chandrasekara, S., Spencer, A., Dear, A. E."Epigenetic regulation of miRNA-124 and multiple downstream targets is associated with treatment response in myeloid malignancies". Oncology Letters 12.3 (2016): 2175-2180.
Chicago
Liu, H., Pattie, P., Chandrasekara, S., Spencer, A., Dear, A. E."Epigenetic regulation of miRNA-124 and multiple downstream targets is associated with treatment response in myeloid malignancies". Oncology Letters 12, no. 3 (2016): 2175-2180. https://doi.org/10.3892/ol.2016.4912
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