miR-150 blocks MLL-AF9-associated leukemia through oncogene repression. Academic Article uri icon


  • UNLABELLED: 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.

published proceedings

  • Mol Cancer Res

author list (cited authors)

  • Bousquet, M., Zhuang, G., Meng, C., Ying, W., Cheruku, P. S., Shie, A. T., ... Zhou, B.

citation count

  • 28

complete list of authors

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

publication date

  • August 2013