Inactivation of dermatopontin via histone deacetylation in human oral cancer

Abstract

ObjectiveDermatopontin (DPT), a regulator of tumoral invasiveness and metastasis, is down-regulated in oral squamous cell carcinoma (OSCC); however, the DPT regulatory mechanism is poorly understood. Epigenetic alterations of chromatin such as histone acetylation do not alter the DNA sequence but modify the chromatin architecture and its accessibility, resulting in repressed gene transcription. MethodsTo investigate whether epigenetic or genetic mechanisms control DPT expression in OSCC, we assessed the effects of a histone deacetylase (HDAC) inhibitor and mutation on DPT expression. Human normal oral keratinocytes and DPT-overexpressed OSCC cells were used for chromatin immunoprecipitation to assess the effects of HDAC inhibitors on DPT expression. ResultsDPT mRNA was significantly (p<0.05) up-regulated in OSCC-derived cells after treatment with HDAC inhibitors, trichostatin A and sodium butyrate, whereas there was no mutation in the entire coding region of the DPT gene. We found significant (p<0.05) enrichment of histone H3 lysine 9 in the DPT promoter region in OSCC-derived cells. ConclusionsThese results suggested that DPT down-regulation in OSCC is associated closely with histone deacetylation and that HDAC inhibitors can reactivate the epigenetically silenced DPT gene.