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

Abstract

<b>Background:</b> Hairy and enhancer of split 1 (Hes-1) protein is a downstream target of Notch signaling andis a basic helix-loop-helix transcriptional repressor. However, definitive evidence for a role in hepatocellularcarcinoma (HCC) cells has not been reported. Here, Hes-1 was revealed to an important component of the Notchsignaling cascade in HCC cell lines possessing different potential for lung metastasis. Materials and <br/><b>Methods</b>:RNAi mediated by plasmid constructs was used to analyze the role of Hes-1 in MHCC-97L HCC cells by assessingproliferation, apoptosis, cell migration and matrigel invasion following transfection. Hes-1 protein expressionanalysis in HCC tissue was also conducted by immunohistochemistry. <br/><b>Results</b>: Our studies revealed that Hes-1was 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 apoptosisand increased migration and invasion. <br/><b>Conclusions</b>: Hes-1 has potential prognostic value in post-surgical HCCpatients and may be an independent prognostic indicator for overall survival and tumor recurrence. Thesefindings have important implications for understanding the mechanisms by which Hes-1 participates in tumorproliferation and invasion.