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Title

Genetic and Epigenetic Silencing of MicroRNA-203 Enhances ABL1 and BCR-ABL1 Oncogene Expression

AuthorsBueno, María J.; Pérez de Castro, Ignacio; Gómez de Cedrón, Marta; Santos, Javier ; Calin, George A.; Cigudosa, Juan C.; Croce, Carlo M.; Fernández-Piqueras, José ; Malumbres, Marcos
KeywordsCell cycle
Issue Date10-Jun-2008
PublisherCell Press
CitationCancer Cell, Volume 13, Issue 6, Pages 496-506, 2008
AbstractThe mammalian genome contains several hundred microRNAs that regulate gene expression through modulation of target mRNAs. Here, we report a fragile chromosomal region lost in specific hematopoietic malignancies. This 7 Mb region encodes about 12% of all genomic microRNAs, including miR-203. This microRNA is additionally hypermethylated in several hematopoietic tumors, including chronic myelogenous leukemias and some acute lymphoblastic leukemias. A putative miR-203 target, ABL1, is specifically activated in these hematopoietic malignancies in some cases as a BCR-ABL1 fusion protein (Philadelphia chromosome). Re-expression of miR-203 reduces ABL1 and BCR-ABL1 fusion protein levels and inhibits tumor cell proliferation in an ABL1-dependent manner. Thus, miR-203 functions as a tumor suppressor, and re-expression of this microRNA might have therapeutic benefits in specific hematopoietic malignancies.
DescriptionSupplemental Data available at http://www.cancercell.org/cgi/content/full/13/6/496/DC1/
Publisher version (URL)http://dx.doi.org/10.1016/j.ccr.2008.04.018
URIhttp://hdl.handle.net/10261/7369
DOI10.1016/j.ccr.2008.04.018
ISSN1535-6108
Appears in Collections:(CBM) Artículos
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