SIRT7 suppresses the epithelial-to-mesenchymal transition in oral squamous cell carcinoma metastasis by promoting SMAD4 deacetylation

Abstract

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most common malignancies and has a poor prognosis. The epithelial-to-mesenchymal transition (EMT) is crucial for increasing the metastasis of OSCC. Recently, studies have indicated that sirtuin7 (SIRT7) is implicated in tumor genesis; however, the potential role of SIRT7 in the EMT and metastasis of OSCC has not been reported. METHODS: We investigated the cellular responses to SIRT7 silencing or overexpression in OSCC cell lines by wound healing assay, migration and invasion assay, western blotting, immunofluorescence and immunohistochemistry. RESULTS: In the present study, we found that SIRT7 was significantly downregulated in OSCC cell lines and human OSCC/OSCC tissues with lymph node metastasis. Overexpression of SIRT7 decreased the proliferation and invasion of OSCC cells in vitro, whereas SIRT7 knockdown significantly increased OSCC cell growth and invasion. Upregulation of SIRT7 concomitantly increased the expression of E-cadherin, and decreased the expression of mesenchymal markers. SIRT7 overexpression also reduced the level of acetylated SMAD4 in OSCC cells. Moreover, SIRT7 overexpression significantly inhibited OSCC lung metastasis in vivo. CONCLUSION: Together, these findings suggested that SIRT7 suppressed EMT in OSCC metastasis by promoting SMAD4 deacetylation.