SEARCH:   Advanced

Blood, 18 June 2009, Vol. 113, No. 25, pp. 6411-6418. Prepublished online as a Blood First Edition Paper on February 11, 2009; DOI 10.1182/blood-2008-07-170589. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-07-170589v1 113/25/6411    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Garzon, R. Articles by Marcucci, G. Search for Related Content PubMed PubMed Citation Articles by Garzon, R. Articles by Marcucci, G. Related Collections Myeloid Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  MYELOID NEOPLASIA MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1 Ramiro Garzon1,2,*, Shujun Liu1,2,*, Muller Fabbri2,3, Zhongfa Liu4, Catherine E.A. Heaphy1,2, Elisa Callegari2,3, Sebastian Schwind1,2, Jiuxia Pang1,2, Jianhua Yu1,2, Natarajan Muthusamy1,2, Violaine Havelange2,3, Stefano Volinia2,3, William Blum1,2, Laura J. Rush5, Danilo Perrotti2,3, Michael Andreeff6, Clara D. Bloomfield1,2, John C. Byrd1,2, Kenneth Chan4, Lai-Chu Wu3,7, Carlo M. Croce2,3, and Guido Marcucci1,2 1 Department of Medicine, 2 Comprehensive Cancer Center, 3 Molecular Virology, Immunology and Medical Genetics, 4 College of Pharmacy, and 5 Department of Veterinary Biosciences, Ohio State University, Columbus; 6 Section of Molecular Hematology and Therapy, Department of Blood and Bone Marrow Transplantation, University of Texas M. D. Anderson Cancer Center, Houston; and 7 Department of Molecular & Cellular Biochemistry, Ohio State University, Columbus Aberrant DNA hypermethylation contributes to myeloid leukemogenesis by silencing structurally normal genes involved in hematopoiesis. MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression by targeting protein-coding mRNAs. Recently, miRNAs have been shown to play a role as both targets and effectors in gene hypermethylation and silencing in malignant cells. In the current study, we showed that enforced expression of miR-29b in acute myeloid leukemia cells resulted in marked reduction of the expression of DNA methyltransferases DNMT1, DNMT3A, and DNMT3B at both RNA and protein levels. This in turn led to decrease in global DNA methylation and reexpression of p15INK4b and ESR1 via promoter DNA hypomethylation. Although down-regulation of DNMT3A and DNMT3B was the result of a direct interaction of miR-29b with the 3' untranslated regions of these genes, no predicted miR-29b interaction sites were found in the DNMT1 3' untranslated regions. Further experiments revealed that miR-29b down-regulates DNMT1 indirectly by targeting Sp1, a transactivator of the DNMT1 gene. Altogether, these data provide novel functional links between miRNAs and aberrant DNA hypermethylation in acute myeloid leukemia and suggest a potentially therapeutic use of synthetic miR-29b oligonucleotides as effective hypomethylating compounds. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: MicroRNA: mIR-ly regulators of DNMT? Elizabeth A. Griffiths and Steven D. Gore Blood 2009 113: 6269-6270. [Abstract] [Full Text] [PDF] This article has been cited by other articles: M. V. Iorio and C. M. Croce MicroRNAs in Cancer: Small Molecules With a Huge Impact J. Clin. Oncol., December 1, 2009; 27(34): 5848 - 5856. [Abstract] [Full Text] [PDF] G. A. Calin and C. M. Croce Chronic lymphocytic leukemia: interplay between noncoding RNAs and protein-coding genes Blood, November 26, 2009; 114(23): 4761 - 4770. [Abstract] [Full Text] [PDF] R. Visone, L. Z. Rassenti, A. Veronese, C. Taccioli, S. Costinean, B. D. Aguda, S. Volinia, M. Ferracin, J. Palatini, V. Balatti, et al. Karyotype-specific microRNA signature in chronic lymphocytic leukemia Blood, October 29, 2009; 114(18): 3872 - 3879. [Abstract] [Full Text] [PDF] E. A. Griffiths and S. D. Gore MicroRNA: mIR-ly regulators of DNMT? Blood, June 18, 2009; 113(25): 6269 - 6270. [Abstract] [Full Text] [PDF]

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020