title: HDAC inhibitors repress BARD1 isoform expression in acute myeloid leukemia cells via activation of miR-19a and/or b.
abstract: Over the past years BARD1 (BRCA1-associated RING domain 1) has been considered as both a BRCA1 (BReast Cancer susceptibility gene 1, early onset) interactor and tumor suppressor gene mutated in breast and ovarian cancers. Despite its role as a stable heterodimer with BRCA1, increasing evidence indicates that BARD1 also has BRCA1-independent oncogenic functions. Here, we investigate BARD1 expression and function in human acute myeloid leukemias and its modulation by epigenetic mechanism(s) and microRNAs. We show that the HDACi (histone deacetylase inhibitor) Vorinostat reduces BARD1 mRNA levels by increasing miR-19a and miR-19b expression levels. Moreover, we identify a specific BARD1 isoform, which might act as tumor diagnostic and prognostic markers.
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Seconda Università degli Studi di Napoli, Naples, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lepore
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Seconda Università degli Studi di Napoli, Naples, Italy ; Institute of Genetics and Biophysics (IGB), Naples, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Dell'Aversana
authors.affiliation: Molecular Gynecology and Obstetrics Laboratory, Department of Gynecology and Obstetrics and Department of Genetic and Laboratory Medicine, University Hospitals of Geneva, HUG, Genève, Switzerland.
authors.forename: Maxim
authors.initials: M
authors.lastname: Pilyugin
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Seconda Università degli Studi di Napoli, Naples, Italy.
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Conte
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Seconda Università degli Studi di Napoli, Naples, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Nebbioso
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Seconda Università degli Studi di Napoli, Naples, Italy.
authors.forename: Floriana
authors.initials: F
authors.lastname: De Bellis
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Seconda Università degli Studi di Napoli, Naples, Italy ; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Francesco P
authors.initials: FP
authors.lastname: Tambaro
authors.affiliation: Division of Hematology and Stem Cell Transplantation Unit, Cardarelli Hospital, Naples, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Izzo
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.affiliation: Division of Hematology and Stem Cell Transplantation Unit, Cardarelli Hospital, Naples, Italy.
authors.forename: Felicetto
authors.initials: F
authors.lastname: Ferrara
authors.affiliation: Molecular Gynecology and Obstetrics Laboratory, Department of Gynecology and Obstetrics and Department of Genetic and Laboratory Medicine, University Hospitals of Geneva, HUG, Genève, Switzerland.
authors.forename: Irmgard
authors.initials: I
authors.lastname: Irminger-Finger
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Seconda Università degli Studi di Napoli, Naples, Italy ; Institute of Genetics and Biophysics (IGB), Naples, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Altucci
mesh_terms: D044127:Epigenesis, Genetic / Q000187:drug effects; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D018922:HL-60 Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D020014:K562 Cells; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D020298:U937 Cells; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis* / Q000235:genetics; D000077337:Vorinostat
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C549214:MIRN19A microRNA, human; D035683:MicroRNAs; D020033:Protein Isoforms; D012334:RNA, Neoplasm; D025521:Tumor Suppressor Proteins; D000077337:Vorinostat; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases