期刊
NATURE GENETICS
卷 43, 期 7, 页码 673-U89出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.858
关键词
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资金
- National Cancer Institute (NCI) [R01-CA142798-01]
- P30 supplemental award
- Louis V. Gerstner Foundation
- William Lawrence and Blanche Hughes (WLBH) Foundation
- Society of MSKCC
- Geoffrey Beene Foundation
- May & Samuel Rudin Foundation
- W.H. Goodwin and A. Goodwin and the Commonwealth Foundation for Cancer Research
- The Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center
- Fund for Scientific Research (FWO) Flanders [G.0198.08, G.0869.10N]
- GOA-UGent [12051203]
- Stichting tegen Kanker
- Belgian Program of Interuniversity Poles of Attraction
- Belgian Foundation Against Cancer
The importance of individual microRNAs (miRNAs) has been established in specific cancers. However, a comprehensive analysis of the contribution of miRNAs to the pathogenesis of any specific cancer is lacking. Here we show that in T-cell acute lymphoblastic leukemia (T-ALL), a small set of miRNAs is responsible for the cooperative suppression of several tumor suppressor genes. Cross-comparison of miRNA expression profiles in human T-ALL with the results of an unbiased miRNA library screen allowed us to identify five miRNAs (miR-19b, miR-20a, miR-26a, miR-92 and miR-223) that are capable of promoting T-ALL development in a mouse model and which account for the majority of miRNA expression in human T-ALL. Moreover, these miRNAs produce overlapping and cooperative effects on tumor suppressor genes implicated in the pathogenesis of T-ALL, including IKAROS (also known as IKZF1), PTEN, BIM, PHF6, NF1 and FBXW7. Thus, a comprehensive and unbiased analysis of miRNA action in T-ALL reveals a striking pattern of miRNA-tumor suppressor gene interactions in this cancer.
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