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Prognostic Significance of Hes-1, a Downstream Target of Notch Signaling in Hepatocellular Carcinoma

  • Zou, Jing-Huai (Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education) ;
  • Xue, Tong-Chun (Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education) ;
  • Sun, Chun (Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education) ;
  • Li, Yan (Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education) ;
  • Liu, Bin-Bin (Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education) ;
  • Sun, Rui-Xia (Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education) ;
  • Chen, Jie (Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education) ;
  • Ren, Zheng-Gang (Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education) ;
  • Ye, Sheng-Long (Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education)
  • Published : 2015.05.18

Abstract

Background: Hairy and enhancer of split 1 (Hes-1) protein is a downstream target of Notch signaling and is a basic helix-loop-helix transcriptional repressor. However, definitive evidence for a role in hepatocellular carcinoma (HCC) cells has not been reported. Here, Hes-1 was revealed to an important component of the Notch signaling cascade in HCC cell lines possessing different potential for lung metastasis. Materials and Methods: RNAi mediated by plasmid constructs was used to analyze the role of Hes-1 in MHCC-97L HCC cells by assessing proliferation, apoptosis, cell migration and matrigel invasion following transfection. Hes-1 protein expression analysis in HCC tissue was also conducted by immunohistochemistry. Results: Our studies revealed that Hes-1 was decreased in HCC cell lines with higher lung metastasis potential at both the mRNA and protein levels. Down-regulation of the Hes-1 gene in MHCC-97L cells resulted in increased cell proliferation, reduced apoptosis and increased migration and invasion. Conclusions: Hes-1 has potential prognostic value in post-surgical HCC patients and may be an independent prognostic indicator for overall survival and tumor recurrence. These findings have important implications for understanding the mechanisms by which Hes-1 participates in tumor proliferation and invasion.

Keywords

References

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