1. MicroRNA-193b-3p acts as a tumor suppressor by targeting the MYB oncogene in T-cell acute lymphoblastic leukemia.
- Author
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Mets, E, Van der Meulen, J, Van Peer, G, Boice, M, Mestdagh, P, Van de Walle, I, Lammens, T, Goossens, S, De Moerloose, B, Benoit, Y, Van Roy, N, Clappier, E, Poppe, B, Vandesompele, J, Wendel, H-G, Taghon, T, Rondou, P, Soulier, J, Van Vlierberghe, P, and Speleman, F
- Subjects
MICRORNA ,ONCOGENES ,T-cell receptor genes ,LYMPHOBLASTIC leukemia ,HEMATOPOIESIS - Abstract
The MYB oncogene is a leucine zipper transcription factor essential for normal and malignant hematopoiesis. In T-cell acute lymphoblastic leukemia (T-ALL), elevated MYB levels can arise directly through T-cell receptor-mediated MYB translocations, genomic MYB duplications or enhanced TAL1 complex binding at the MYB locus or indirectly through the TAL1/miR-223/FBXW7 regulatory axis. In this study, we used an unbiased MYB 3′untranslated region-microRNA (miRNA) library screen and identified 33 putative MYB-targeting miRNAs. Subsequently, transcriptome data from two independent T-ALL cohorts and different subsets of normal T-cells were used to select miRNAs with relevance in the context of normal and malignant T-cell transformation. Hereby, miR-193b-3p was identified as a novel bona fide tumor-suppressor miRNA that targets MYB during malignant T-cell transformation thereby offering an entry point for efficient MYB targeting-oriented therapies for human T-ALL. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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