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.
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Mets
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Van der Meulen
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Van Peer
authors.affiliation: Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Boice
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Mestdagh
authors.affiliation: Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, Ghent, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Van de Walle
authors.affiliation: Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Lammens
authors.affiliation: VIB/Department for Molecular Biomedical Research, Ghent University, Ghent, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Goossens
authors.affiliation: Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: De Moerloose
authors.affiliation: Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium.
authors.forename: Y
authors.initials: Y
authors.lastname: Benoit
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: N
authors.initials: N
authors.lastname: Van Roy
authors.affiliation: Genome Rearrangements and Cancer Laboratory, U462 INSERM, Laboratoire Central d'Hématologie and Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Clappier
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Poppe
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Vandesompele
authors.affiliation: Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: H-G
authors.initials: HG
authors.lastname: Wendel
authors.affiliation: Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, Ghent, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Taghon
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Rondou
authors.affiliation: Genome Rearrangements and Cancer Laboratory, U462 INSERM, Laboratoire Central d'Hématologie and Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Soulier
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Van Vlierberghe
authors.affiliation: Center for Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Speleman
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism; D000073979:F-Box-WD Repeat-Containing Protein 7; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D015698:Genomic Library; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D059467:Transcriptome; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D044767:Ubiquitin-Protein Ligases; C513273:FBXW7 protein, human; C546818:MIRN193 microRNA, human; C525067:MIR223, human; C067143:TAL1 protein, human