ZEB1 promotes tumorigenesis and metastasis in hepatocellular carcinoma by regulating the expression of vimentin

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and its prognosis remains poor. Epithelial-to-mesenchymal transition (EMT)-induced markers have emerged as key regulators of tumor development and progression in HCC. The aim of the present study was to investigate the role of zinc finger E-box-binding homeobox 1 (ZEB1) in the tumorigenesis of HCC and to elucidate the mechanism underlying the correlation between ZEB1 and vimentin (VIM). The expression levels of ZEB1 and VIM were assessed by immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction analysis in HCC tissues and cell lines. The biological significance of ZEB1 was examined by downregulating the expression of ZEB1 in Huh-7 cells. A luciferase reporter assay was used to investigate the association between ZEB1 and VIM. The expression levels of ZEB1 and VIM were higher in tumor tissues compared with those in adjacent normal tissues, and they were significantly associated with a poor prognosis in patients with HCC, whereas ZEB1 silencing led to the attenuation of HCC cell proliferation, invasion and migration. Furthermore, it was observed that ZEB1 was able to bind to a certain site in the VIM promoter and regulate the transcriptional activity of VIM. Therefore, the present study demonstrated that ZEB1 is a potential biomarker of the tumorigenesis and progression of HCC, and it may regulate transcription of the VIM gene.