1. A cooperative microRNA-tumor suppressor gene network in acute T-cell lymphoblastic leukemia (T-ALL).
- Author
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Mavrakis KJ, Van Der Meulen J, Wolfe AL, Liu X, Mets E, Taghon T, Khan AA, Setty M, Rondou P, Vandenberghe P, Delabesse E, Benoit Y, Socci NB, Leslie CS, Van Vlierberghe P, Speleman F, and Wendel HG
- Subjects
- Adolescent, Adult, Animals, Apoptosis, Biomarkers, Tumor genetics, Blotting, Western, Cell Line, Tumor, Cell Proliferation, Child, Child, Preschool, Female, Fluorescent Antibody Technique, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Immunoenzyme Techniques, Infant, Luciferases metabolism, Male, Mice, MicroRNAs metabolism, Oligonucleotide Array Sequence Analysis, RNA, Messenger genetics, Reverse Transcriptase Polymerase Chain Reaction, Survival Rate, Young Adult, Gene Regulatory Networks, Genes, Tumor Suppressor, MicroRNAs genetics, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma genetics
- 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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