HDAC inhibitors repress BARD1 isoform expression in acute myeloid leukemia cells via activation of miR-19a and/or b

Ilaria Lepore; Carmela Dell'Aversana; Maxim Pilyugin; Mariarosaria Conte; Angela Nebbioso; Floriana De Bellis; Francesco P Tambaro; Tiziana Izzo; Guillermo Garcia-Manero; Felicetto Ferrara; Irmgard Irminger-Finger; Lucia Altucci

doi:10.1371/journal.pone.0083018

HDAC inhibitors repress BARD1 isoform expression in acute myeloid leukemia cells via activation of miR-19a and/or b

PLoS One. 2013 Dec 11;8(12):e83018. doi: 10.1371/journal.pone.0083018. eCollection 2013.

Affiliations

¹ Department of Biochemistry, Biophysics and General Pathology, Seconda Università degli Studi di Napoli, Naples, Italy.
² Department of Biochemistry, Biophysics and General Pathology, Seconda Università degli Studi di Napoli, Naples, Italy ; Institute of Genetics and Biophysics (IGB), Naples, Italy.
³ Molecular Gynecology and Obstetrics Laboratory, Department of Gynecology and Obstetrics and Department of Genetic and Laboratory Medicine, University Hospitals of Geneva, HUG, Genève, Switzerland.
⁴ 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.
⁵ Division of Hematology and Stem Cell Transplantation Unit, Cardarelli Hospital, Naples, Italy.
⁶ Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Epigenesis, Genetic / drug effects
Gene Expression Regulation, Leukemic / drug effects*
HL-60 Cells
Histone Deacetylase Inhibitors / pharmacology*
Humans
Hydroxamic Acids / pharmacology*
K562 Cells
Leukemia, Myeloid, Acute / drug therapy
Leukemia, Myeloid, Acute / genetics
Leukemia, Myeloid, Acute / metabolism*
MicroRNAs / genetics
MicroRNAs / metabolism*
Protein Isoforms / biosynthesis
Protein Isoforms / genetics
RNA, Neoplasm / genetics
RNA, Neoplasm / metabolism*
Tumor Suppressor Proteins / biosynthesis*
Tumor Suppressor Proteins / genetics
U937 Cells
Ubiquitin-Protein Ligases / biosynthesis*
Ubiquitin-Protein Ligases / genetics
Vorinostat

Substances

Histone Deacetylase Inhibitors
Hydroxamic Acids
MIRN19 microRNA, human
MicroRNAs
Protein Isoforms
RNA, Neoplasm
Tumor Suppressor Proteins
Vorinostat
BARD1 protein, human
Ubiquitin-Protein Ligases

Grants and funding

Grant Support. This work was supported by EU: Blueprint (contract no. 282510); Italian IHEC (Flag Project: EPIGEN); the Italian Association for Cancer Research (AIRC no.11812); Italian Ministry of University and Research (PRIN_2009PX2T2E_004); PON0101227; Swiss National Research Foundations (NF 3100A0-122353), Ligue SuisseContre le Cancer (KLS 01962-10-2006), and LigueGenevoiseContre le Cancer (LGCC 1117) to IIF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.