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Blood. 2011 Aug 18;118(7):1899-902. doi: 10.1182/blood-2010-09-306258. Epub 2011 Jun 17.

MicroRNA29a regulates the expression of the nuclear oncogene Ski.

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1
Department of Hematology, Oncology and Immunology, Philipps University of Marburg, Medical Center of the University Giessen and Marburg, Marburg, Germany.

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.

PMID:
21685371
DOI:
10.1182/blood-2010-09-306258
[Indexed for MEDLINE]
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