title: miR-194-5p/BCLAF1 deregulation in AML tumorigenesis.
abstract: Deregulation of epigenetic mechanisms, including microRNA, contributes to leukemogenesis and drug resistance by interfering with cancer-specific molecular pathways. Here, we show that the balance between miR-194-5p and its newly discovered target BCL2-associated transcription factor 1 (BCLAF1) regulates differentiation and survival of normal hematopoietic progenitors. In acute myeloid leukemias this balance is perturbed, locking cells into an immature, potentially 'immortal' state. Enhanced expression of miR-194-5p by treatment with the histone deacetylase inhibitor SAHA or by exogenous miR-194-5p expression re-sensitizes cells to differentiation and apoptosis by inducing BCLAF1 to shuttle between nucleus and cytosol. miR-194-5p/BCLAF1 balance was found commonly deregulated in 60 primary acute myeloid leukemia patients and was largely restored by ex vivo SAHA treatment. Our findings link treatment responsiveness to re-instatement of miR-194-5p/BCLAF1 balance.
authors.affiliation: Institute of Genetics and Biophysics, CNR, Naples, Italy.|Department of Biochemistry, Biophysics and General Pathology, Universitá degli studi della Campania-Luigi Vanvitelli, Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Dell'Aversana
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Universitá degli studi della Campania-Luigi Vanvitelli, Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Giorgio
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Universitá degli studi della Campania-Luigi Vanvitelli, Naples, Italy.
authors.forename: L
authors.initials: L
authors.lastname: D'Amato
authors.affiliation: Institute of Genetics and Biophysics, CNR, Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Lania
authors.affiliation: Faculty of Science, Department of Molecular Biology, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Matarese
authors.affiliation: Faculty of Science, Department of Molecular Biology, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands.|Centre for Research in Molecular Medicine, The University of Lahore, Lahore, Pakistan.
authors.forename: S
authors.initials: S
authors.lastname: Saeed
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Universitá degli studi della Campania-Luigi Vanvitelli, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Di Costanzo
authors.affiliation: Umberto I Hospital, Salerno, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Belsito Petrizzi
authors.affiliation: Umberto I Hospital, Salerno, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Ingenito
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Universitá degli studi della Campania-Luigi Vanvitelli, Naples, Italy.|Faculty of Science, Department of Molecular Biology, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands.
authors.forename: J H A
authors.initials: JHA
authors.lastname: Martens
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Pallavicini
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Minucci
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Universitá degli studi della Campania-Luigi Vanvitelli, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Carissimo
authors.affiliation: Faculty of Science, Department of Molecular Biology, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands.
authors.forename: H G
authors.initials: HG
authors.lastname: Stunnenberg
authors.affiliation: Institute of Genetics and Biophysics, CNR, Naples, Italy.|Department of Biochemistry, Biophysics and General Pathology, Universitá degli studi della Campania-Luigi Vanvitelli, Naples, Italy.
authors.forename: L
authors.identifier: 0000-0002-7312-5387
authors.initials: L
authors.lastname: Altucci
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C119386:BCLAF1 protein, human; C554846:MIRN194 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins