HDAC inhibitors target HDAC5, upregulate microRNA-125a-5p, and induce apoptosis in breast cancer cells.

ABSTRACT: Histone deacetylase inhibitors (HDACi) are novel clinical anticancer drugs that inhibit HDAC gene expression and induce cell apoptosis in human cancers. Nevertheless, the detailed mechanism or the downstream HDAC targets by which HDACi mediates apoptosis in human breast cancer cells remains unclear. Here, we show that HDACi reduce tumorigenesis and induce intrinsic apoptosis of human breast cancer cells through the microRNA miR-125a-5p in vivo and in vitro. Intrinsic apoptosis was activated by the caspase 9/3 signaling pathway. In addition, HDACi mediated the expression of miR-125a-5p by activating RUNX3/p300/HDAC5 complex. Subsequently, miR-125a-5p silenced HDAC5 post-transcriptionally in the cells treated with HDACi. Thus, a regulatory loop may exist in human breast cancer cells involvin

SUBMITTER: Hsieh TH 

PROVIDER: S-EPMC4395776 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature