Abstract
MicroRNAs (miRNAs) are short single-stranded RNAs that have a potentially important role in gene regulation. Using a quantitative real-time polymerase chain reaction assay specific to the mature miRNA, the expression level of a selected group of haematopoietic tissue-specific miRNAs was measured across a set of 30 primary adult acute myeloid leukaemia (AML) with a normal karyotype. The expression levels of each miRNA were correlated with the genome-wide mRNA expression profiles in the same leukaemias. This revealed that miR-181a correlated strongly with the AML morphological sub-type and with the expression of genes previously identified through sequence analysis as potential interaction targets. Three other miRNAs, miR-10a, miR-10b and miR-196a-1, showed a clear correlation with HOX gene expression.
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References
Bartel DP . MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116: 281–297.
Doench JG, Sharp PA . Specificity of microRNA target selection in translational repression. Genes Dev 2004; 18: 504–511.
Mansfield JH, Harfe BD, Nissen R, Obenauer J, Srineel J, Chaudhuri A et al. MicroRNA-responsive ‘sensor’ transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression. Nat Genet 2004; 36: 1079–1083.
Yekta S, Shih IH, Bartel DP . MicroRNA-directed cleavage of HOXB8 mRNA. Science 2004; 304: 594–596.
Bagga S, Bracht J, Hunter S, Massirer K, Holtz J, Eachus R et al. Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell 2005; 122: 553–563.
Jing Q, Huang S, Guth S, Zarubin T, Motoyama A, Chen J et al. Involvement of microRNA in AU-rich element-mediated mRNA instability. Cell 2005; 120: 623–634.
Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A et al. RAS is regulated by the let-7 microRNA family. Cell 2005; 120: 635–647.
Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 2005; 433: 769–773.
Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 2004; 101: 2999–3004.
Calin GA, Croce CM . MicroRNAs and chromosomal abnormalities in cancer cells. Oncogene 2006; 25: 6202–6210.
Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 2002; 99: 15524–15529.
Michael MZ, SM OC, van Holst Pellekaan NG, Young GP, James RJ . Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res 2003; 1: 882–891.
Metzler M, Wilda M, Busch K, Viehmann S, Borkhardt A . High expression of precursor microRNA-155/BIC RNA in children with Burkitt lymphoma. Genes Chromosomes Cancer 2004; 39: 167–169.
Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 2004; 64: 3753–3756.
Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G et al. Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun 2005; 334: 1351–1358.
Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA 2005; 102: 13944–13949.
Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res 2005; 65: 7065–7070.
Pallante P, Visone R, Ferracin M, Ferraro A, Berlingieri MT, Troncone G et al. MicroRNA deregulation in human thyroid papillary carcinomas. Endocr Relat Cancer 2006; 13: 497–508.
Roldo C, Missiaglia E, Hagan JP, Falconi M, Capelli P, Bersani S et al. MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol 2006; 24: 4677–4684.
Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 2006; 9: 189–198.
Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D et al. MicroRNA expression profiles classify human cancers. Nature 2005; 435: 834–838.
Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT et al. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 2005; 33: e179.
Debernardi S, Lillington DM, Chaplin T, Tomlinson S, Amess J, Rohatiner A et al. Genome-wide analysis of acute myeloid leukemia with normal karyotype reveals a unique pattern of homeobox gene expression distinct from those with translocation-mediated fusion events. Genes Chromosomes Cancer 2003; 37: 149–158.
Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR et al. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol 1976; 33: 451–458.
Griffiths-Jones S . miRBase: the microRNA sequence database. Methods Mol Biol 2006; 342: 129–138.
Chen CZ, Li L, Lodish HF, Bartel DP . MicroRNAs modulate hematopoietic lineage differentiation. Science 2004; 303: 83–86.
Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB . Prediction of mammalian microRNA targets. Cell 2003; 115: 787–798.
John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS . Human MicroRNA Targets. PLoS Biol 2004; 2: e363.
Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ et al. Combinatorial microRNA target predictions. Nat Genet 2005; 37: 495–500.
Lagos-Quintana M, Rauhut R, Meyer J, Borkhardt A, Tuschl T . New microRNAs from mouse and human. RNA 2003; 9: 175–179.
Lim LP, Glasner ME, Yekta S, Burge CB, Bartel DP . Vertebrate microRNA genes. Science 2003; 299: 1540.
Ramkissoon SH, Mainwaring LA, Ogasawara Y, Keyvanfar K, McCoy Jr JP, Sloand EM et al Hematopoietic-specific microRNA expression in human cells. Leuk Res 2006; 30: 643–647.
Smalheiser NR, Torvik VI . A population-based statistical approach identifies parameters characteristic of human microRNA-mRNA interactions. BMC Bioinformatics 2004; 5: 139.
Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ . miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res 2006; 34: D140–144.
Lewis BP, Burge CB, Bartel DP . Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005; 120: 15–20.
Garzon R, Pichiorri F, Palumbo T, Iuliano R, Cimmino A, Aqeilan R et al. MicroRNA fingerprints during human megakaryocytopoiesis. Proc Natl Acad Sci USA 2006; 103: 5078–5083.
Scheijen B, Griffin JD . Tyrosine kinase oncogenes in normal hematopoiesis and hematological disease. Oncogene 2002; 21: 3314–3333.
Thorsteinsdottir U, Sauvageau G, Hough MR, Dragowska WH, Lansdorp P, Lawrence HJ et al. Overexpression of HOXA10 in murine hematopoietic cells perturbs both myeloid and lymphoid differentiation and leads to acute myeloid leukemia. Mol Cell Biol 1997; 17: 495–505.
Thorsteinsdottir U, Mamo A, Kroon E, Jerome L, Bijl J, Lawrence HJ et al. Overexpression of the myeloid leukemia-associated Hoxa9 gene in bone marrow cells induces stem cell expansion. Blood 2002; 99: 121–129.
Acknowledgements
We gratefully acknowledge D Lillington for karyotype analysis and Professor TA Lister for clinical support. This work has been supported by grants from the Kay Kendall Leukaemia Fund and the Barts and London Charitable Foundation.
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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)
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Debernardi, S., Skoulakis, S., Molloy, G. et al. MicroRNA miR-181a correlates with morphological sub-class of acute myeloid leukaemia and the expression of its target genes in global genome-wide analysis. Leukemia 21, 912–916 (2007). https://doi.org/10.1038/sj.leu.2404605
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DOI: https://doi.org/10.1038/sj.leu.2404605
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