MicroRNA-150 down Regulation in Acute Myeloid Leukaemia Patients and Its Prognostic Implication

Authors

  • Dalia Adel Abdelhalim Department of Clinical and Chemical Pathology, Medical Division, National Research Centre, Cairo, Egypt
  • Basma M. Elgamal Department of Clinical Pathology, National Cancer Institute, Cairo University, Cairo, Egypt
  • Mona R. ElKafoury Department of Clinical and Chemical Pathology, Medical Division, National Research Centre, Cairo, Egypt
  • Naglaa M. Hassan Department of Clinical Pathology, National Cancer Institute, Cairo University, Cairo, Egypt
  • Marwa M. Hussein Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt
  • Mahmoud M. Elhefnawi Informatics and System Department, Engineering Research Division, National Research Centre, Cairo, Egypt
  • Asmaa M. Elfiky Environmental and Occupational Medicine Department, Environmental Research Division, National Research Centre, Cairo, Egypt
  • Mohammad N. Hamdy Department of Clinical and Chemical Pathology, Medical Division, National Research Centre, Cairo, Egypt

DOI:

https://doi.org/10.3889/oamjms.2018.420

Keywords:

Acute myeloid leukaemia, microRNA, biomarkers, miR-150, leukemogenesis

Abstract

BACKGROUND: MicroRNAs (miRNAs) are small, non-coding RNAs that are important for post-transcriptional gene regulation in both healthy and morbid conditions. Numerous miRNAs promote tumorigenesis, while others have a tumour suppressive effects. Acute myeloid leukaemia (AML) is a heterogeneous group of genetically diverse hematopoietic malignancies with variable response to treatment.

AIM: Our study aimed to investigate the possible role of miR-150 in de novo adult AML and the impact of its level on survival, and we used in the silicon analysis to predict the main target genes involved in miR-150 mediated cancer pathway.

MATERIAL AND METHODS: We evaluated miR-150 expression profiling assay using TaqMan primer probes RT-PCR in the plasma of 50 adult AML patients, before the start of treatment and at day 28 of treatment, along with 20 normal adult control samples. miR-16 was used as an endogenous reference for standardisation. Follow-up of patients during treatment at day 28 of induction chemotherapy and after one year was done.

RESULTS: In this study, we found a significantly lower level of miR-150 in AML patients when compared to controls (p = 0.005) with 0.62 fold change than in healthy controls. Patients were divided into two groups: the low miR-150 group (miR-150 < 1) and the high miR-150 group (miR-150 > 1). A statistically significant difference was found between the two groups regarding initial total leukocytic count and initial PB blast count while for the TLC, HB and PLT count at follow up. No difference in the overall survival between the low and the high miR-150 groups could be demonstrated.

CONCLUSION: Our results suggest that miR-150 functions as a tumour suppressor and gatekeeper in inhibiting cell transformation and that its downregulation is required for leukemogenesis.

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References

Dohner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015; 373:1136–1152. https://doi.org/10.1056/NEJMra1406184 PMid:26376137

Papaemmanuil E, Dohner H, Campbell PJ. Genomic classification in acute myeloid leukemia. N Engl J Med. 2016; 375:900–901. https://doi.org/10.1056/NEJMc1608739

De Kouchkovsky I, Abdul-Hay M. Acute myeloid leukemia: A comprehensive review and 2016 update. Blood Cancer J. 2016; 6: e441. https://doi.org/10.1038/bcj.2016.50 PMid:27367478 PMCid:PMC5030376

Vitsios DM, Davis MP, van Dongen S, Enright AJ. Large-scale analysis of microRNA expression, epi-transcriptomic features and biogenesis. Nucleic Acids Res. 2017; 45:1079–1090. https://doi.org/10.1093/nar/gkw1031 PMid:28180281 PMCid:PMC5388392

Wallace JA, O'Connell RM. MicroRNAs and acute myeloid leukemia: Therapeutic implications and emerging concepts. Blood. 2017; 130:1290–1301. https://doi.org/10.1182/blood-2016-10-697698 PMid:28751524 PMCid:PMC5600138

Ambros V. microRNAs: tiny regulators with great potential. Cell. 2001; 107 (7): 823–6. https://doi.org/10.1016/S0092-8674(01)00616-X

Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell. 2005; 123 (4): 631–40. https://doi.org/10.1016/j.cell.2005.10.022 PMid:16271387

Edelstein LC, Bray PF. MicroRNAs in platelet production and activation. Blood. 2011; 117(20): 5289–96. https://doi.org/10.1182/blood-2011-01-292011 PMid:21364189 PMCid:PMC3109704

Vasilatou D, Papageorgiou S, Pappa V, Papageorgiou E, Dervenoulas J. The role of microRNAs in normal and malignant hematopoiesis. European Journal of Haematology. 2010; 84 (1): 1–16. https://doi.org/10.1111/j.1600-0609.2009.01348.x PMid:19744129

Lulla RR, Costa FF, Bischof JM, Chou PM, Bonaldo MF, Vanin EF, Soares MB. Identification of Differentially Expressed MicroRNAs in Osteosarcoma. Sarcoma. 2011; 732690. https://doi.org/10.1155/2011/732690

Mraz M, Chen L, Rassenti LZ, Ghia EM, Li H, Jepsen K, Smith EN, Messer K, Frazer KA, Kipps TJ. miR-150 influences B-cell receptor signaling in chronic lymphocytic leukemia by regulating expression of GAB1 and FOXP1. Blood. 2014; 124(1): 84–95. https://doi.org/10.1182/blood-2013-09-527234 PMid:24787006 PMCid:PMC4125356

Morris V, Zhang A, Yang T, Derek L, Stirewalt, Ramamurthy R, Meshinchi S, Vivian G. Oehler. MicroRNA-150 expression induces myeloid differentiation of human acute leukemia cells and normal hematopoietic precursors. PLoS One. 2013; 8(9): e75815. https://doi.org/10.1371/journal.pone.0075815 PMid:24086639 PMCid:PMC3782459

Jiang X, Huang H, Li Z, Li Y, Wang X, Gurbuxani S et al. Blockade of miR-150 maturation by MLL-fusion/MYC/LIN-28 is required for MLL-associated leukemia. Cancer Cell. 2012; 22(4):524–535. https://doi.org/10.1016/j.ccr.2012.08.028 PMid:23079661 PMCid:PMC3480215

Fayyad-Kazan H, Bitar N, Najar M, Lewalle P, Fayyad-Kazan M, Badran R et al. Circulating miR-150 and miR-342 in plasma are novel potential biomarkers for acute myeloid leukemia. J Transl Med. 2013; 11: 31. https://doi.org/10.1186/1479-5876-11-31 PMid:23391324 PMCid:PMC3579719

Dweep H, Sticht C, Pandey P, Gretz N. miRWalk-database: prediction of possible miRNA binding sites by "walking" the genes of three genomes. JBI. 2011; 44 (5): 839–47. https://doi.org/10.1016/j.jbi.2011.05.002

Dweep, H. and N. Gretz, miRWalk2.0. A comprehensive atlas of microRNA-target interactions. Nat Methods. 2015; 12(8): 697. https://doi.org/10.1038/nmeth.3485 PMid:26226356

Dennis Jr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki, RA. "DAVID: Database for Annotation, Visualization, and Integrated Discovery". Genome Biology. 2003;4 (5): P3. https://doi.org/10.1186/gb-2003-4-5-p3

Huang DW, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nature Protocols. 2009; 4(1):44–57. https://doi.org/10.1038/nprot.2008.211 PMid:19131956

Kanehisa M, Goto S. "KEGG: Kyoto Encyclopedia of Genes and Genomes". Nucleic Acids Res. 2000; 28 (1): 27–30. https://doi.org/10.1093/nar/28.1.27 PMid:10592173 PMCid:PMC102409

Wang XS, Gong JN, Yu J, Wang F, Zhang XH et al. MicroRNA-29a and microRNA-142-3p are regulators of myeloid differentiation and acute myeloid leukemia. Blood 2012; 119:4992-5004. https://doi.org/10.1182/blood-2011-10-385716 PMid:22493297

Vitsios DM, Davis MP, van Dongen S, Enright AJ. Large-scale analysis of microRNA expression, epi-transcriptomic features and biogenesis. Nucleic (2013) Acids Res. 2017; 45:1079–1090. https://doi.org/10.1093/nar/gkw1031 PMid:28180281 PMCid:PMC5388392

Li Y, Gao L, Luo X, Wang L, Gao X et al. Epigenetic silencing of microRNA-193a contributes to leukemogenesis in t (8;21) acute myeloid leukemia by activating the PTEN/PI3K signal pathway. Blood 121: 499-509. https://doi.org/10.1182/blood-2012-07-444729 PMid:23223432

Wang Y, Wang J, Yin Z, Zhang W, Hu X, Wang Y. Serum miR-150 as a novel prognostic biomarker for acute myeloid leukemia. Int J Clin Exp Pathol. 2017; 10(6):6906-6911.

Xu DD, Zhou PJ, Wang Y, Zhang Y, Zhang R, Zhang L, Chen SH, Fu WY, Ruan BB, Xu HP, et al. miR-150 suppresses the proliferation and tumorigenicity of leukemia stem cells by targeting the Nanog signaling pathway. Front Pharmacol. 2016; 7:439. https://doi.org/10.3389/fphar.2016.00439 PMid:27917123 PMCid:PMC5114241

Morris VA, Cummings CL, Korb B, Boaglio S, Oehler VG. Deregulated KLF4 expression in myeloid leukemias alters cell proliferation and differentiation through microRNA and gene targets. Mol Cell Biol. 2015; 36: 559-573. https://doi.org/10.1128/MCB.00712-15 PMid:26644403 PMCid:PMC4751692

Watanabe A, Tagawa H, Yamashita J, Teshima K, Nara M, Iwamoto K, et al. The role of microRNA-150 as a tumor suppressor in malignant lymphoma. Leukemia. 2011; 25:1324–1334. https://doi.org/10.1038/leu.2011.81 PMid:21502955

Bousquet, Marina, et al. miR-150 blocks MLL-AF9–associated leukemia through oncogene repression. Molecular Cancer Research. 2013; 11(8): 912-922. https://doi.org/10.1158/1541-7786.MCR-13-0002-T PMid:23604034

Fleischmann K, Pagel P, von Frowein J, Magg T, Roscher AA, Schmid I. The leukemogenic fusion gene MLL-AF9 alters microRNA expression pattern and inhibits monoblastic differentiation via miR511 repression. Journal of Experimental & Clinical Cancer Research 2016; 35:9. https://doi.org/10.1186/s13046-016-0283-5 PMid:26762252 PMCid:PMC4712549

Fang ZH, Wang SL, Zhao JT, Lin Z J, et al. miR-150 exerts antileukemia activity in vitro and in vivo through regulating genes in multiple pathways. Cell death & disease. 2016; 7(9):e2371. https://doi.org/10.1038/cddis.2016.256 PMid:27899822 PMCid:PMC5059860

Fernandez N, Cordiner RA, Young RS, Hug N, Macias S, Caceres JF. Genetic variation and RNA structure regulate microRNA biogenesis. Nat Commun. 2017; 8:15114. https://doi.org/10.1038/ncomms15114 PMid:28466845 PMCid:PMC5418625

Wallace JA, O'Connell RM. MicroRNAs and acute myeloid leukemia: Therapeutic implications and emerging concepts. Blood. 2017; (130):1290–1301. https://doi.org/10.1182/blood-2016-10-697698 PMid:28751524 PMCid:PMC5600138

Trino S, Lamorte D, Caivano A, Laurenzana I, Tagliaferri D, Falco G, et al. MicroRNAs as New Biomarkers for Diagnosis and Prognosis, and as Potential Therapeutic Targets in Acute Myeloid Leukemia. Int J Mol Sci. 2018; 19:460. https://doi.org/10.3390/ijms19020460 PMid:29401684 PMCid:PMC5855682

Published

2018-11-19

How to Cite

1.
Abdelhalim DA, Elgamal BM, ElKafoury MR, Hassan NM, Hussein MM, Elhefnawi MM, Elfiky AM, Hamdy MN. MicroRNA-150 down Regulation in Acute Myeloid Leukaemia Patients and Its Prognostic Implication. Open Access Maced J Med Sci [Internet]. 2018 Nov. 19 [cited 2024 Mar. 28];6(11):1993-2000. Available from: https://oamjms.eu/index.php/mjms/article/view/oamjms.2018.420

Issue

Section

A - Basic Science