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- Title
A cooperative microRNA-tumor suppressor gene network in acute T-cell lymphoblastic leukemia (T-ALL).
- Authors
Mavrakis, Konstantinos J.; Van Der Meulen, Joni; Wolfe, Andrew L.; Xiaoping Liu; Mets, Evelien; Taghon, Tom; Khan, Aly A.; Setti, Manu; Rondou, Pieter; Vandenberghe, Peter; Delabesse, Eric; Benoit, Yves; Socci, Nicholas B.; Leslie, Christina S.; Van Vlierberghe, Pieter; Speleman, Frank; Wendel, Hans-Guido
- Abstract
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.
- Subjects
RNA; CANCER; CARCINOGENESIS; TUMORS; GENES
- Publication
Nature Genetics, 2011, Vol 43, Issue 7, p673
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.858