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Mol Cancer Res. 2013 Aug;11(8):912-22. doi: 10.1158/1541-7786.MCR-13-0002-T. Epub 2013 Apr 19.

miR-150 blocks MLL-AF9-associated leukemia through oncogene repression.

Author information

1
Department of Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA.

Abstract

The microRNA miR-150, a critical regulator of hematopoiesis, is downregulated in mixed-lineage leukemia (MLL). In this study, miR-150 acts as a potent leukemic tumor suppressor by blocking the oncogenic properties of leukemic cells. By using MLL-AF9-transformed cells, we demonstrate that ectopic expression of miR-150 inhibits blast colony formation, cell growth, and increases apoptosis in vitro. More importantly, ectopic expression of miR-150 in MLL-AF9-transformed cells completely blocked the development of myeloid leukemia in transplanted mice. Furthermore, gene expression profiling revealed that miR-150 altered the expression levels of more than 30 "stem cell signature" genes and many others that are involved in critical cancer pathways. In addition to the known miR-150 target Myb, we also identified Cbl and Egr2 as bona fide targets and shRNA-mediated suppression of these genes recapitulated the pro-apoptotic effects observed in leukemic cells with miR-150 ectopic expression. In conclusion, we demonstrate that miR-150 is a potent leukemic tumor suppressor that regulates multiple oncogenes.

IMPLICATIONS:

These data establish new, key players for the development of therapeutic strategies to treat MLL-AF9-related leukemia.

PMID:
23604034
DOI:
10.1158/1541-7786.MCR-13-0002-T
[Indexed for MEDLINE]
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