期刊
CELL
卷 158, 期 3, 页码 593-606出版社
CELL PRESS
DOI: 10.1016/j.cell.2014.05.049
关键词
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资金
- NIH/NCI [P30 CA016087-30]
- Chair's Grant [U10 CA98543]
- National Cancer Institute, National Institutes of Health (Bethesda, MD, USA) [U24 CA114766]
- National Institutes of Health [1RO1CA133379, 1RO1CA105129, 1RO1CA149655, 5RO1CA173636, 5RO1CA169784, 1RO1GM088847, 5T32CA009161-37, 5T32GM0072-38]
- William Lawrence and Blanche Hughes Foundation
- Leukemia & Lymphoma Society [6340-11, 6373-13]
- Chemotherapy Foundation
- Irma T. Hirschl Trust
- V Foundation for Cancer Research
- St. Baldrick's Foundation
- American Society of Hematology fellowship
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 IncRNA genes, a fraction of which are directly controlled by the Notch1/Rpbjk 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 IncRNAs are important downstream targets of the Notch signaling pathway, and additionally they are key regulators of the oncogenic state in T-ALL.
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