Abstract
BackgroundHistone deacetylase (HDAC) inhibitors are widely used in clinical investigation as novel drug targets. For example, panobinostat and vorinostat have been used to treat patients with melanoma. However, HDAC inhibitors are small-molecule compounds without a specific target, and their mechanism of action is unclear. Therefore, it is necessary to investigate which HDACs are required for the proliferation and metastasis of melanoma cells.MethodsWe used overexpression and knocking down lentivirus to clarify the influence of HDAC5 and HDAC6 in melanoma development. Also, we introduced stable HDAC5 or HDAC6 knockdown cells into null mice and found that the knockdown cells were unable to form solid tumors. Finally, we tested HDAC5 and HDAC6 expression and sub-location in clinical melanoma tissues and tumor adjacent tissues.ResultsIn this study, and found that HDAC5 and HDAC6 were highly expressed in melanoma cells but exhibited low expression levels in normal skin cells. Furthermore, we knocked down HDAC5 or HDAC6 in A375 cells and demonstrated that both HDAC5 and HDAC6 contributed to the proliferation and metastasis of melanoma cells.ConclusionsThis study demonstrated both HDAC5 and HDAC6 were required for melanoma cell proliferation and metastasis through different signaling pathways.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0753-0) contains supplementary material, which is available to authorized users.
Highlights
Histone deacetylase (HDAC) inhibitors are widely used in clinical investigation as novel drug targets
HDAC5 and HDAC6 are overexpressed in melanoma cells For effective prevention of melanoma development using HDAC inhibitors, further study of the exact mechanisms for inhibition of HDACs is very important
To assess the high expression of HDACs in melanoma cells comparing with normal skin cells, we tested the expression of all HDACs at the protein and mRNA levels
Summary
Histone deacetylase (HDAC) inhibitors are widely used in clinical investigation as novel drug targets. Panobinostat and vorinostat have been used to treat patients with melanoma. It is necessary to investigate which HDACs are required for the proliferation and metastasis of melanoma cells. Some agents have emerged as inhibitors of histone deacetylases (HDACs), with consequences of chromosome remodeling, cell cycle arrest and selective toxicity to melanoma cells comparing with normal melanocytes. Vorinostat and romidepsin, have been approved by the FDA to treat refractory cutaneous T cell lymphoma [8,9,10].
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