ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. It has been reported that HCC has a poor prognosis. In the majority of cases, once metastatic, HCC is incurable. To identify an effective treatment for HCC, it is important to understand the underlying molecular mechanisms of HCC?associated occurrence, proliferation, metastasis and carcinogenesis. In the present study, the role of Up?frameshift 1 (UPF1), a potential tumor suppressor, was investigated in the HCC cell lines. The expression levels of UPF1 in an HCC cell line were examined by reverse transcription?quantitative polymerase chain reaction. The expression levels of 19 key proteins in numerous signaling pathways were detected via protein array analysis in the presence of UPF1 overexpression. The present study further investigated the effects of UPF1 expression levels on the epithelial?mesenchymal transition (EMT) process by targeting E?cadherin, N?cadherin, Vimentin and Twist?related protein 1 (Twist). The results of the present study revealed that UPF1 was significantly downregulated in an HCC cell line. The majority of the proteins exhibited upregulated expression levels in the presence of UPF1 overexpression in the HCC cell line, Huh?7. Key proteins, including cluster of differentiation (CD)31 (platelet endothelial cell adhesion molecule?1), Vimentin, CD44, PCNA, Ki?67, N?Cadherin, Survivin, P53, Met and retinoblastoma exhibited a significant association with UPF1. Furthermore, western blotting indicated that the expression levels of N?cadherin, Vimentin and Twist were notably upregulated while UPF1 was overexpressed; however, E?cadherin was downregulated and opposing observations were reported with protein array analysis. In summary, E?cadherin expression levels were regulated by the manifold, and UPF1, a potential tumor suppressor, may promote the EMT process in Huh?7 HCC cells. The findings of the present study suggested that UPF1 expression levels affected the EMT process by targeting E?cadherin, N?cadherin, Vimentin and Twist.
