Report
Genome-wide RNA-mediated interference screen identifies miR-19 targets in Notch-induced T-cell acute lymphoblastic leukaemia
| العنوان: | Genome-wide RNA-mediated interference screen identifies miR-19 targets in Notch-induced T-cell acute lymphoblastic leukaemia |
|---|---|
| المؤلفون: | Mavrakis, K. J., Wolfe, A. L., Oricchio, E., Palomero, T., de Keersmaecker, K., McJunkin, K., Zuber, J., James, T., Chang, K., Khan, A. A., Leslie, C. S., Parker, J. S., Paddison, P. J., Tam, W., Ferrando, A., Wendel, H. G. |
| سنة النشر: | 2010 |
| المجموعة: | Cold Spring Harbor Laboratory: CSHL Institutional Repository |
| مصطلحات موضوعية: | cancer, leukemia, miRNA, mutations |
| الوصف: | MicroRNAs (miRNAs) have emerged as novel cancer genes. In particular, the miR-17-92 cluster, containing six individual miRNAs, is highly expressed in haematopoietic cancers and promotes lymphomagenesis in vivo. Clinical use of these findings hinges on isolating the oncogenic activity within the 17-92 cluster and defining its relevant target genes. Here we show that miR-19 is sufficient to promote leukaemogenesis in Notch1-induced T-cell acute lymphoblastic leukaemia (T-ALL) in vivo. In concord with the pathogenic importance of this interaction in T-ALL, we report a novel translocation that targets the 17-92 cluster and coincides with a second rearrangement that activates Notch1. To identify the miR-19 targets responsible for its oncogenic action, we conducted a large-scale short hairpin RNA screen for genes whose knockdown can phenocopy miR-19. Strikingly, the results of this screen were enriched for miR-19 target genes, and include Bim (Bcl2L11), AMP-activated kinase (Prkaa1) and the phosphatases Pten and PP2A (Ppp2r5e). Hence, an unbiased, functional genomics approach reveals a coordinate clampdown on several regulators of phosphatidylinositol-3-OH kinase-related survival signals by the leukaemogenic miR-19. |
| نوع الوثيقة: | report |
| اللغة: | unknown |
| Relation: | Mavrakis, K. J., Wolfe, A. L., Oricchio, E., Palomero, T., de Keersmaecker, K., McJunkin, K., Zuber, J., James, T., Chang, K., Khan, A. A., Leslie, C. S., Parker, J. S., Paddison, P. J., Tam, W., Ferrando, A., Wendel, H. G. (April 2010) Genome-wide RNA-mediated interference screen identifies miR-19 targets in Notch-induced T-cell acute lymphoblastic leukaemia. Nature Cell Biology, 12 (4). 372-U159. ISSN 1465-7392 |
| DOI: | 10.1038/ncb2037 |
| الاتاحة: | https://repository.cshl.edu/id/eprint/15477/ http://www.ncbi.nlm.nih.gov/pubmed/20190740 https://doi.org/10.1038/ncb2037 |
| رقم الانضمام: | edsbas.95FADE75 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/ncb2037 |
|---|