1. A cooperative microRNA-tumor suppressor gene network in acute T-cell lymphoblastic leukemia (T-ALL)
- Author
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Nicholas B Socci, Franki Speleman, Andrew Wolfe, Eric Delabesse, Yves Benoit, Manu Setty, Xiaoping Liu, Pieter Rondou, Pieter Van Vlierberghe, Joni Van der Meulen, Christina S. Leslie, Aly A. Khan, Peter Vandenberghe, Tom Taghon, Evelien Mets, Konstantinos J. Mavrakis, and Hans-Guido Wendel
- Subjects
Adult ,Male ,Adolescent ,Tumor suppressor gene ,Blotting, Western ,Fluorescent Antibody Technique ,Apoptosis ,Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ,Article ,Immunoenzyme Techniques ,Mice ,Young Adult ,RNA interference ,Cell Line, Tumor ,microRNA ,Biomarkers, Tumor ,Genetics ,medicine ,Animals ,Humans ,Gene silencing ,PTEN ,Gene Regulatory Networks ,Genes, Tumor Suppressor ,RNA, Messenger ,Child ,Luciferases ,Cell Proliferation ,Oligonucleotide Array Sequence Analysis ,Regulation of gene expression ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Infant ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Survival Rate ,Gene expression profiling ,MicroRNAs ,Leukemia ,Child, Preschool ,biology.protein ,Cancer research ,Female - 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.
- Published
- 2011
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