Targeting miRNAs by histone deacetylase inhibitors (HDACi): Rationalizing epigenetics-based therapies for breast cancer.

MicroRNAs (miRNAs) belong to a group of short RNA molecules of ~22 nucleotides that play a significant role in the regulation of gene expression through post-transcriptional regulatory mechanisms. They can directly interact with their target mRNA molecules and induce target gene silencing. Many investigations over the past decade have revealed the involvement of different miRNAs in essential biological events. The expression of a considerable number of miRNAs is tightly regulated through epigenetic events such as histone modifications and DNA methylation. Notably, irregularities in these epigenetic events are associated with aberrant expression of miRNAs in a range of diseases including cancer. Impaired epigenetic events associated with aberrant expression of miRNAs can be pharmacologically modified using chromatin modifying drugs. Numerous pre-clinical and clinical data demonstrate that histone deacetylase inhibitors (HDACi) can re-establish the expression of aberrantly expressed miRNAs in a range of cancer types, rationalizing miRNAs as potential drug targets. This review highlights evidence from investigations assessing the effects of different classes of HDACi on miRNA expression in breast cancer (BC).