Experiments with small interfering RNA (siRNA) implicated HDAC1 in the regulation of proliferation and survival of cancer cells. In particular, the idea that HDAC1 can also be a potential target for therapeutic intervention in certain cancers stems from a series of studies. HDAC1 has been shown to inhibit estrogen receptor alpha protein expression and transcriptional activity, suggesting that it can modulate breast cancer progression. Overexpression of HDAC1 at mRNA and protein levels was reported for human gastric and prostate cancers. Furthermore, published data indicate a role of mouse HDAC1 in the regulation of proliferation and development. For instance, the expression of HDAC1 is induced upon growth factor activation of mouse T cells and fibroblasts and HDAC1 levels were found to be elevated in highly proliferative tissues, embryonic stem (ES) cells, and several transformed cell lines , suggesting a link between HDAC1 function and proliferation. In accordance with this idea, disruption of the HDAC1 gene resulted in reduced proliferation of mouse embryos and ES cells, whereas overexpression of HDAC1 led to impaired cell proliferation of murine fibroblasts. Taken together, these results suggest that class I HDACs are crucial in controlling the proliferation state of mammalian cells.
West A C, Johnstone R W. New and emerging HDAC inhibitors for cancer treatment[J]. The Journal of clinical investigation, 2014, 124(1): 30-39.