title: Complexity of miR-223 regulation by CEBPA in human AML.
abstract: microRNA-223 (miR-223) can trigger normal granulopoiesis. miR-223 expression is regulated by two distinct CEBPA (CCAAT/enhancer binding protein-alpha) sites. Here, we report that miR-223 is largely suppressed in cells from acute myeloid leukemia (AML) patients. By sequencing, we found that miR-223 suppression in AML is not caused by DNA sequence alterations, nor is it mediated by promoter hypermethylation. The analysis of the individual contribution of both CEBPA sites to miR-223 regulation identified the site upstream of the miR-223 primary transcript as the predominant regulatory element. Our results suggest that miR-223 suppression in AML is caused by impaired miR-223 upstream factors.
authors.affiliation: Institute of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 10, 3010 Bern, Switzerland.
authors.forename: Marianne
authors.initials: M
authors.lastname: Eyholzer
authors.forename: Sabine
authors.initials: S
authors.lastname: Schmid
authors.forename: Julian A
authors.initials: JA
authors.lastname: Schardt
authors.forename: Simon
authors.initials: S
authors.lastname: Haefliger
authors.forename: Beatrice U
authors.initials: BU
authors.lastname: Mueller
authors.forename: Thomas
authors.initials: T
authors.lastname: Pabst
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D015870:Gene Expression; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D035683:MicroRNAs; C515848:CEBPA protein, human; C525067:MIR223, human