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Title: Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression.
Authors: Bueno MJ; Perez de Castro I; Gomez de Cedron M; Santos J; Calin GA; Cigudosa JC; Croce CM; Fernandez-Piqueras J; Malumbres M
Journal: Cancer Cell
Volume: 13
Issue: 6
Year: 2008
Pages: 496-506
Abstract: The 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.
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J:138632  Mouse Genome Informatics
18538733  National Library of Medicine/PubMed