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Title: Genome-wide RNAi screen identifies miR-19 targets in Notch-induced acute T-cell leukaemia (T-ALL)      
keywords:
Transcriptome or Gene expression
ID:
PRJNA124343
description:
MicroRNAs (miRNAs) have emerged as novel cancer genes. In particular, the 17~92 cluster of miRNAs is highly expressed in haematopoietic cancers and promotes lymphomagenesis in vivo1,2. 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 lymphoblastic leukaemia (T-ALL) in vivo. Consistent with the pathogenic importance of this interaction, we report a novel translocation targeting the 17~92 miRNA cluster coinciding with a second rearrangement that activates Notch1 in T-ALL. To identify the miR-19 targets responsible for its oncogenic action, we conducted a large-scale short-hairpin RNA (shRNA) screen for genes whose knockdown could phenocopy miR-19. Strikingly, the results of this screen were enriched for miR-19 target genes, and included Bim (Bcl2L11)1,3, AMP-activated kinase (Prkaa1), and the tumour suppressor phosphatases Pten and PP2A (Ppp2r5e). Hence, an unbiased, functional genomics approach reveals a coordinate clamp down on several regulators of PI3K-related survival signals by the leukaemogenic miR-19. Overall design: Gene expression data revealing differences in gene expression between parental FL5-12 cells transduced with Vector and miR-19 expressing FL5-12 cells
accesstypes:
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA124343
authentication:
none
authorization:
none
ID:
pmid:20190740
dateReleased:
01-30-2010
name:
Mus musculus
ncbiID:
ncbitax:10090
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject
  • R01CA120196,/CA/NCI NIH HHS/United States

  • P30 DK056465/DK/NIDDK NIH HHS/United States

  • R01 CA142798/CA/NCI NIH HHS/United States

  • R01 CA120196/CA/NCI NIH HHS/United States

  • R01 CA142798-01/CA/NCI NIH HHS/United States

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