Overexpression of SIRT1 promotes metastasis through epithelial-mesenchymal transition in hepatocellular carcinoma

BMC Cancer

Research Article

Li Zhang¹  Peng-Xi Zhu¹  Chong Hao²  Xue Yang²  Xu-Guang Zhang²  Li-Xin Wei²  Zhi-Peng Han²  Chen Zong²  Wen-Ting Liu²  Qiu-Dong Zhao²  Ting-Ting Fan²  Jing-Hua Jiang² 

[1] Department of Pharmacy, Chang Hai Hospital, the Second Military Medical University, 168 Changhai Road, 200433, Shanghai, China;Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, 200438, Shanghai, China;

关键词: SIRT1;    Human hepatocellular carcinoma;    Metastasis;    Epithelial-mesenchymal transition;   

DOI  :  10.1186/1471-2407-14-978

 received in 2014-06-20, accepted in 2014-12-12,  发布年份 2014

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Hao et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.