| Literature DB >> 25083870 |
Thomas Trimarchi1, Erhan Bilal2, Panagiotis Ntziachristos1, Giulia Fabbri3, Riccardo Dalla-Favera3, Aristotelis Tsirigos4, Iannis Aifantis5.
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.Entities:
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Year: 2014 PMID： 25083870 PMCID： PMC4131209 DOI： 10.1016/j.cell.2014.05.049
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582