title: Overexpression of SIRT1 promotes metastasis through epithelial-mesenchymal transition in hepatocellular carcinoma.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Western 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.
  
  
  RESULTS
  SIRT1 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.
  
  
  CONCLUSIONS
  Our data suggest that SIRT1 may play an important role in HCC progression and could be a potential molecular therapy target for HCC.
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China. haochong2006@126.com.
authors.forename: Chong
authors.initials: C
authors.lastname: Hao
authors.affiliation: Department of Pharmacy, Chang Hai Hospital, the Second Military Medical University, 168 Changhai Road, Shanghai, 200433, China. zhupengxi5905@sina.cn.
authors.forename: Peng-Xi
authors.initials: PX
authors.lastname: Zhu
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China. yangxue19900307@126.com.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China. hanzhipeng0311@126.com.
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: Han
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China. wajjh1978@163.com.
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Jiang
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China. chenchen_z1@126.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Zong
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China. xgzh1985@aliyun.com.
authors.forename: Xu-Guang
authors.initials: XG
authors.lastname: Zhang
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China. liuwenting1015@163.com.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Liu
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China. zhaoqd@gmail.com.
authors.forename: Qiu-Dong
authors.initials: QD
authors.lastname: Zhao
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China. funtingting@126.com.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Fan
authors.affiliation: Department of Pharmacy, Chang Hai Hospital, the Second Military Medical University, 168 Changhai Road, Shanghai, 200433, China. zhanglicdma@189.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China. weilixin_smmu@163.com.
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Wei
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D009362:Neoplasm Metastasis; D034622:RNA Interference; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D056564:Sirtuin 1