Class I histone deacetylase inhibition is synthetic lethal with BRCA1 deficiency in breast cancer cells.

ABSTRACT: Breast cancer susceptibility gene 1 (BRCA1) is a tumor suppressor gene, which is frequently mutated in breast and ovarian cancers. BRCA1 plays a key role in the homologous recombination directed DNA repair, allowing its deficiency to act as a therapeutic target of DNA damaging agents. In this study, we found that inhibition of the class I histone deacetylases (HDAC) exhibited synthetic lethality with BRCA1 deficiency in breast cancer cells. Transcriptome profiling and validation study showed that HDAC inhibition enhanced the expression of thioredoxin interaction protein (TXNIP), causing reactive oxygen species (ROS)-mediated DNA damage. This effect induced preferential apoptosis in BRCA1 ^-/- breast cancer cells where DNA repair system is compromised. Two animal exp

SUBMITTER: Zhang B 

PROVIDER: S-EPMC7161709 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature