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

Index: PLoS ONE 8 , e83018, (2013)

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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.