TY - JOUR
T1 - Genome-wide mapping and characterization of notch-regulated long noncoding RNAs in acute leukemia
AU - Trimarchi, Thomas
AU - Bilal, Erhan
AU - Ntziachristos, Panagiotis
AU - Fabbri, Giulia
AU - Dalla-Favera, Riccardo
AU - Tsirigos, Aristotelis
AU - Aifantis, Iannis
PY - 2014/7/31
Y1 - 2014/7/31
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84905401266&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84905401266&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2014.05.049
DO - 10.1016/j.cell.2014.05.049
M3 - Article
C2 - 25083870
AN - SCOPUS:84905401266
SN - 0092-8674
VL - 158
SP - 593
EP - 606
JO - Cell
JF - Cell
IS - 3
ER -
