MiR-150 blocks MLL-AF9-associated leukemia through oncogene repression

Marina Bousquet, Guoqing Zhuang, Cong Meng, Wei Ying, Patali S. Cheruku, Andrew T. Shie, Stephanie Wang, Guangtao Ge, Piu Wong, Gang Wang, Stephen Safe, Beiyan Zhou

Research output: Contribution to journalArticle

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)912-922
Number of pages11
JournalMolecular Cancer Research
Volume11
Issue number8
DOIs
StatePublished - Aug 2013
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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