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Sp1/NFkappaB/HDAC/miR-29b regulatory network in KIT-driven myeloid leukemia.
- Source :
-
Cancer cell [Cancer Cell] 2010 Apr 13; Vol. 17 (4), pp. 333-47. - Publication Year :
- 2010
-
Abstract
- The biologic and clinical significance of KIT overexpression that associates with KIT gain-of-function mutations occurring in subsets of acute myeloid leukemia (AML) (i.e., core binding factor AML) is unknown. Here, we show that KIT mutations lead to MYC-dependent miR-29b repression and increased levels of the miR-29b target Sp1 in KIT-driven leukemia. Sp1 enhances its own expression by participating in a NFkappaB/HDAC complex that further represses miR-29b transcription. Upregulated Sp1 then binds NFkappaB and transactivates KIT. Therefore, activated KIT ultimately induces its own transcription. Our results provide evidence that the mechanisms of Sp1/NFkappaB/HDAC/miR-29b-dependent KIT overexpression contribute to leukemia growth and can be successfully targeted by pharmacological disruption of the Sp1/NFkappaB/HDAC complex or synthetic miR-29b treatment in KIT-driven AML.<br /> (Copyright 2010 Elsevier Inc. All rights reserved.)
- Subjects :
- Cell Line, Tumor
Chromosomes, Human, Pair 7 genetics
Gene Expression Regulation, Neoplastic
Genetic Vectors
Homeostasis
Humans
Leukemia, Myeloid physiopathology
Transcription, Genetic
Histone Deacetylases physiology
Immunoglobulins physiology
Leukemia, Myeloid genetics
MicroRNAs physiology
NF-kappa B physiology
Proto-Oncogene Proteins c-kit genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1878-3686
- Volume :
- 17
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cancer cell
- Publication Type :
- Academic Journal
- Accession number :
- 20385359
- Full Text :
- https://doi.org/10.1016/j.ccr.2010.03.008