Abstract
BackgroundSIRT1 is a member of the mammalian sirtuin family with the ability to deacetylate histone and nonhistone proteins. The correlation between SIRT1 expression and tumor metastasis in several types of cancer has aroused widespread concern. This study investigated SIRT1 expression and its prognostic value in hepatocellular carcinoma (HCC). The function of SIRT1 in hepatocarcinogenesis was further investigated in cell culture and mouse models.MethodsWestern blotting and immunohistochemistry were used to explore SIRT1 expression in HCC cell lines and primary HCC clinical specimens. The functions of SIRT1 in the migration and invasion in the HCC cell line were analyzed by infecting cells with adenovirus containing full-length SIRT1 or sh-RNA. The effect of SIRT1 on tumorigenicity in nude mice was also investigated.ResultsSIRT1 expression was significantly overexpressed in the tumor tissues and HCC cell lines. SIRT1 significantly promoted the ability of migration and invasion in HCC cells. In addition, experiments with a mouse model revealed that SIRT1 overexpression enhanced HCC tumor metastasis in vivo. Furthermore, we demonstrated that SIRT1 significantly enhanced the invasive and metastatic potential by inducing epithelial-mesenchymal transition in HCC cells. A clinicopathological analysis showed that SIRT1 expression was significantly correlated with tumor size, tumor number, and TNM staging. Kaplan–Meier survival curves revealed that positive SIRT1 expression was associated with poor prognosis in patients with HCC.ConclusionsOur data suggest that SIRT1 may play an important role in HCC progression and could be a potential molecular therapy target for HCC.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-978) contains supplementary material, which is available to authorized users.
Highlights
SIRT1 is a member of the mammalian sirtuin family with the ability to deacetylate histone and nonhistone proteins
Increased SIRT1 expression promoted migration and invasion in hepatocellular carcinoma (HCC) cell lines We determined SIRT1 expression using a panel of HCC cell lines
Western blotting results showed that the SIRT1 protein was overexpressed in the HCC cell lines (SMMC-7721, HepG2, Hep3B and Huh-7; Figure 1A)
Summary
SIRT1 is a member of the mammalian sirtuin family with the ability to deacetylate histone and nonhistone proteins. The correlation between SIRT1 expression and tumor metastasis in several types of cancer has aroused widespread concern. This study investigated SIRT1 expression and its prognostic value in hepatocellular carcinoma (HCC). The function of SIRT1 in hepatocarcinogenesis was further investigated in cell culture and mouse models. Liver cancer is the fifth most frequently diagnosed cancer and the second leading cause of cancer deaths worldwide. Hepatocellular carcinoma (HCC) is the most common primary liver malignancy in adults, accounting for 70–. Modifiable risk factors, including chronic hepatitis B virus or hepatitis C virus infection, aflatoxin B1, and alcohol are thought to be the main causes of HCC [1]. A thorough understanding of the underlying mechanisms of tumor metastasis is vital for effective prevention and therapeutics in the field of liver cancer research
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