Supplementary Figures 1 - 6 from miR-150 Blocks MLL-AF9–Associated Leukemia through Oncogene Repression

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

doi:10.1158/1541-7786.22509880.v1

15417786mcr130002t-sup-mcr-13-0002-tfig1-6.pdf (146.37 kB)

Supplementary Figures 1 - 6 from miR-150 Blocks MLL-AF9–Associated Leukemia through Oncogene Repression

journal contribution

posted on 2023-04-03, 16:05 authored by 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

PDF file - 146K, Figure S1. Analysis of microRNA profiles in various MLL-associated leukemias. Figure S2. Analysis of MLL-AF9 expression cells transformed from bone marrow stem/progenitors. Figure S3. Phenotypic analysis of leukemia from mice transplanted with MLL-AF9 cells. Figure S4. Quantitative PCR analysis of miR-150 expression in various cell types. Figure S5. Wild type and mutated binding sites of miR-150 in Myb luciferase constructs. Figure S6. Wild type and mutated binding sites of miR-150 in CBL and Egr2 luciferase constructs.

History

ARTICLE 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. Mol Cancer Res; 11(8); 912–22. ©2013 AACR.