Histone deacetylase 7 silencing induces apoptosis and autophagy in salivary mucoepidermoid carcinoma cells

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Mucoepidermoid carcinoma (MEC) is the most frequent type of salivary gland malignancy and affects both minor and major salivary glands 1. Surgical excision is the standard treatment for all grades of MEC, and adjunctive postoperative radiotherapy is available for high‐grade MECs. However, patients with unresectable and metastatic MEC have poor long‐term clinical outcomes, and no targeted therapy is currently available 2. Therefore, the development of targeted chemotherapy for MEC may represent alternative treatment options and improve patient outcomes 3.
Epigenetic mechanisms play an important role in the initiation of tumors by regulating tumor‐related gene expression 4. Histone deacetylases (HDACs) are key enzymes involved in epigenetic modulation and catalyze the removal of acetyl from lysine residues in histones and non‐histone proteins, causing gene transcriptional repression and subsequent changes in signaling events 5. The HDAC family contains 18 isoenzymes that are grouped into classes I, II, III, and IV, based on their homology to respective yeasts and has been identified in mammals 6. Aberrant activation of HDACs leads to transcriptional repression of diverse genes mainly involved in the regulation of behavior of tumor cells such as proliferation, cell cycle progression, apoptosis, and invasion 7. HDAC overexpression has been reported in various types of cancer, including oral cancer 8. Therefore, HDAC inhibition has been recognized as a new class of therapeutic tools for cancer in recent years. HDAC inhibitors causes growth arrest and apoptosis in oral cancer cells, and induction of chromatin acetylation by HDAC inhibitor reduces chemoresistance of MEC cells through cancer stem cells destruction 9. However, little is known on the expression pattern and contribution of specific HDAC isoforms to tumor growth and progression is still unclear in particular cancers. Multiple HDAC inhibitors have been developed as cancer therapeutics. The identification of HDAC isoform‐specific inhibitors will provide a better understanding of the role of individual HDACs, as well as potential new opportunities for developing useful drugs 11. Our previous study showed that HDAC inhibitor apicidin effectively inhibited cell growth in MEC cells 12. However, it remains unknown which members of the HDAC family are selectively reduced by apicidin treatment and strongly related to the regulation of MEC cell proliferation. In this study, we investigated the specific inhibition of HDAC7 expression in apicidin‐treated MEC cells and examined the effect of a specific siRNA for HDAC7 on cell proliferation, apoptosis, and autophagy to clarify the specific roles of HDACs in MEC cells.
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