github link
Accession IconGSE20097

Genome-wide RNAi screen identifies miR-19 targets in Notch-induced acute T-cell leukaemia (T-ALL)

Organism Icon Mus musculus
Sample Icon 6 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)

Submitter Supplied Information

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.
PubMed ID
Total Samples
6
Submitter’s Institution

Samples

Show of 0 Total Samples
Filter
Add/Remove
Accession Code
Title
Cell line
Processing Information
Additional Metadata
No rows found
Loading...