title: miR-150 blocks MLL-AF9-associated leukemia through oncogene repression.
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.
  
  
  CONCLUSIONS
  These data establish new, key players for the development of therapeutic strategies to treat MLL-AF9-related leukemia.
authors.affiliation: Department of Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Bousquet
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zhuang
authors.forename: Cong
authors.initials: C
authors.lastname: Meng
authors.forename: Wei
authors.initials: W
authors.lastname: Ying
authors.forename: Patali S
authors.initials: PS
authors.lastname: Cheruku
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Shie
authors.forename: Stephanie
authors.initials: S
authors.lastname: Wang
authors.forename: Guangtao
authors.initials: G
authors.lastname: Ge
authors.forename: Piu
authors.initials: P
authors.lastname: Wong
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Stephen
authors.initials: S
authors.lastname: Safe
authors.forename: Beiyan
authors.initials: B
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D051767:Early Growth Response Protein 2 / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D016147:Genes, Tumor Suppressor; D057809:HEK293 Cells; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D009857:Oncogenes; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics / Q000378:metabolism; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
chemical_list: D051767:Early Growth Response Protein 2; D035683:MicroRNAs; D015514:Oncogene Proteins, Fusion; D050721:Proto-Oncogene Proteins c-cbl; D020598:Proto-Oncogene Proteins c-myb; C497327:Egr2 protein, mouse; C533097:MIR150, human; C551356:MLL-AF9 fusion protein, mouse; C493849:Cbl protein, mouse