Impact of Histone Deacetylase Inhibitors on microRNA Expression and Cancer Therapy: A Review.

Saira Ali, Karen Humphreys, Ross McKinnon, Michael Michael

    Research output: Contribution to journalArticle

    20 Citations (Scopus)

    Abstract

    Preclinical Research Chromatin-modifying drugs, such as histone deacetylase inhibitors (HDACi), have shown potential as cancer therapeutics, either alone or in combination with other therapies. HDACi have the ability to reverse aberrant epigenetic modifications associated with cancer, namely dysregulated histone acetylation. There are currently three FDA approved HDACi; vorinostat, romidepsin, and panobinostat. Epigenetic modifications can regulate the expression of protein coding genes, and in addition can alter expression of microRNA (miRNA) genes. Many miRNAs play key roles in cell proliferation and apoptosis, and are commonly dysregulated in cancer states. A number of in vitro and in vivo studies have demonstrated the ability of chromatin-modifying drugs to alter miRNA expression, which may provide the basis for further investigation of miRNAs as therapeutic targets or as biomarkers of drug response. This review summarises findings from studies investigating the effects of HDACi on miRNA expression, as well as key clinical trials involving HDACi. Understanding how chromatin-modifying drugs epigenetically modulate miRNA genes provides further insight into the cellular mechanisms that deliver therapeutic responses, and may assist in refining treatment strategies. Drug Dev Res 76: 296-317, 2015.

    Original languageEnglish
    Pages (from-to)296-317
    Number of pages22
    JournalDrug Development Research
    Volume76
    Issue number6
    DOIs
    Publication statusPublished - 2015

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