We found that SIRT1 mRNA levels were drastically undere pressed in 14 of the 21 OSCC samples com pared with e pression in their matched normal tissues. We ne t used immunohistochemistry techniques to analyze the levels of SIRT1 e pression in clinical samples. We found that 15 pairs of matched normal and tumor tissue samples obtained from 21 OSCC patients showed significantly higher SIRT1 e pression in the normal tissue as compared to the tumor tissue. These results suggested that SIRT1 might e clusively be responsible for the development of oral cancer, and that decreasing SIRT1 e pression and enzyme activity may increase an individuals susceptibility to tumorigenesis and metastasis of oral cancer.

SIRT1 represses migration and invasion of OSCC cells through its deacetylase activity SIRT1 is a histone protein deacetylase, and numerous studies have reported SIRT1 involvement in the regula tion of various processes through its deacetylase activity. Therefore, we conducted Boyden Chamber assays to determine whether the deacetylase activity of SIRT1 would suppress the migration and invasion of oral can cer cells. As e pected, activation of SIRT1 in OSCC cell lines by resveratrol suppressed the migration of OECM1 and HSC3 cells. In contrast, an SIRT1 antagonist was completely ineffective in suppressing cell migration, and greatly increased oral cancer cell metastasis in vitro. Ne t, we ectopically e pressed SIRT1 in OSCC cell lines OECM1 and HSC3, thus taking advantage of their low SIRT1 e pression.

As shown in Figure 2B, overe pression of SIRT1 induced by transient transfection significantly blocked the migration and invasion of OSCC cells, as compared with the migration and invasion behaviors shown by pEGFP C1 vector only transfected control cells. Furthermore, we also knocked down SIRT1 e pres sion in both OSCC cell lines with or without siRNA oligonucleotides, and found that knockdown cells dis played significantly increased migration and invasion abil ities, compared with those shown by Scrambled control cells. These results indicated that the migration and invasion of OSCC cells were significantly suppressed by e ogenous overe pression of SIRT1, while repression of SIRT1 by small interfering RNA molecules increased the metastatic potential of OSCC cells.

Thus, SIRT1 acti vation appears to be tightly correlated with cell migration and invasion Entinostat ability, and SIRT1 might be an important regulator of migration and invasion in oral cancer cells. SIRT1 regulates e pression of epithelial and mesenchymal protein markers Previous studies have described E cadherin as a well established hallmark of EMT. Therefore, we sought to determine whether E cadherin e pression is altered in OSCC cell lines. Surprisingly, we found that SIRT1 and E cadherin were overe pressed in HOK cell lines com pared to their e pression in both OSCC cell lines.