Format

Send to

Choose Destination
Cell. 2014 Jul 31;158(3):593-606. doi: 10.1016/j.cell.2014.05.049.

Genome-wide mapping and characterization of Notch-regulated long noncoding RNAs in acute leukemia.

Author information

1
Howard Hughes Medical Institute, Laura and Isaac Perlmutter Cancer Center, and Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA; Department of Pathology, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA.
2
Computational Biology Center, IBM Thomas J. Watson Research Center, 1101 Kitchawan Road, Yorktown Heights, NY 10598, USA.
3
Institute for Cancer Genetics and the Herbert Irving Comprehensive Cancer Center, Columbia University, 1130 St. Nicholas Avenue, New York, NY 10032, USA.
4
Department of Pathology, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA; Center for Health Informatics and Bioinformatics, NYU School of Medicine, 227 East 30(th) Street, New York, NY 10016, USA. Electronic address: aristotelis.tsirigos@nyumc.org.
5
Howard Hughes Medical Institute, Laura and Isaac Perlmutter Cancer Center, and Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA; Department of Pathology, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA. Electronic address: iannis.aifantis@nyumc.org.

Abstract

Notch signaling is a key developmental pathway that is subject to frequent genetic and epigenetic perturbations in many different human tumors. Here we investigate whether long noncoding RNA (lncRNA) genes, in addition to mRNAs, are key downstream targets of oncogenic Notch1 in human T cell acute lymphoblastic leukemia (T-ALL). By integrating transcriptome profiles with chromatin state maps, we have uncovered many previously unreported T-ALL-specific lncRNA genes, a fraction of which are directly controlled by the Notch1/Rpbjκ activator complex. Finally we have shown that one specific Notch-regulated lncRNA, LUNAR1, is required for efficient T-ALL growth in vitro and in vivo due to its ability to enhance IGF1R mRNA expression and sustain IGF1 signaling. These results confirm that lncRNAs are important downstream targets of the Notch signaling pathway, and additionally they are key regulators of the oncogenic state in T-ALL.

PMID:
25083870
PMCID:
PMC4131209
DOI:
10.1016/j.cell.2014.05.049
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center