Authors: | 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.; Speleman, F. |
Article Title: | MicroRNA-193b-3p acts as a tumor suppressor by targeting the MYB oncogene in T-cell acute lymphoblastic leukemia |
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. © 2015 Macmillan Publishers Limited. |
Keywords: | controlled study; human tissue; unclassified drug; human cell; major clinical study; nonhuman; cancer patient; t lymphocyte; animal cell; gene targeting; microrna; gene expression; cohort analysis; gene locus; gene function; in vivo study; in vitro study; acute lymphoblastic leukemia; tumor suppressor gene; 3' untranslated region; tumor suppressor protein; malignant transformation; transcriptome; t cell leukemia; t lymphocyte subpopulation; peptide library; oncogene myb; protein myb; human; priority journal; article; t cell acute lymphoblastic leukemia; microrna 193b 3p |
Journal Title: | Leukemia |
Volume: | 29 |
Issue: | 4 |
ISSN: | 0887-6924 |
Publisher: | Nature Publishing Group |
Date Published: | 2015-04-01 |
Start Page: | 798 |
End Page: | 806 |
Language: | English |
DOI: | 10.1038/leu.2014.276 |
PROVIDER: | scopus |
PUBMED: | 25231743 |
PMCID: | PMC4890642 |
DOI/URL: | |
Notes: | Export Date: 4 May 2015 -- Source: Scopus |