title: MicroRNA29a regulates the expression of the nuclear oncogene Ski.
abstract: MicroRNAs (miRNAs) are small, noncoding RNA molecules that regulate growth and differentiation. miRNAs are frequently located at cancer-specific fragile sites in the human genome, such as chromosome 7q. The nuclear oncogene SKI is up-regulated in acute myeloid leukemia (AML) with -7/del7q. Here we asked whether loss of miRNAs on chromosome 7q may explain this up-regulation. miR-29a expression was found to be down-regulated in AML with -7/del7q. Forced expression of miR-29a down-regulated Ski and its target gene, Nr-CAM, whereas miR-29a inhibition induced Ski expression. Luciferase assays validated a functional binding site for miR-29a in the 3' untranslated region of SKI. Finally, in samples of AML patients, we observed an inverse correlation of Ski and miR-29a expression, respectively. In conclusion, up-regulation of Ski in AML with -7/del7q is caused by loss of miR-29a. miR-29a may therefore function as an important tumor suppressor in AML by restraining expression of the SKI oncogene.
authors.affiliation: Department of Hematology, Oncology and Immunology, Philipps University of Marburg, Medical Center of the University Giessen and Marburg, Marburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Teichler
authors.forename: Thomas
authors.initials: T
authors.lastname: Illmer
authors.forename: Josephine
authors.initials: J
authors.lastname: Roemhild
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Ovcharenko
authors.forename: Thorsten
authors.initials: T
authors.lastname: Stiewe
authors.forename: Andreas
authors.initials: A
authors.lastname: Neubauer
mesh_terms: D020413:3' Untranslated Regions; D045744:Cell Line, Tumor; D002897:Chromosomes, Human, Pair 7; D004268:DNA-Binding Proteins / Q000235:genetics*; D015536:Down-Regulation; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C060614:SKI protein, human