UNC119 promotes the growth and migration of hepatocellular carcinoma via Wnt/β-catenin and TGF-β/EMT signaling pathways.

PURPOSE: It has been reported that UNC119 is significantly up-regulated in liver cancer cells. However, the role of UNC119 in liver cancer and the clinical significance of reducing its expression in hepatocellular carcinoma (HCC) are not well understood. The aim of this study was to investigate the expression profile of UNC119 in HCC and its connection with the progression of HCC.

METHODS: UNC119 expression in HCC cell lines and tissues was assessed using quantitative real-time PCR, western blot and immunohistochemical analyses. The biological functions of UNC119 during the proliferation, growth and other different life cycles of tumor cells were also analyzed both in vitro and in vivo.

RESULTS: UNC119 expression was up-regulated in both HCC cell lines and tissues. A higher level of UNC119 not only promoted HCC cell proliferation, but also enhanced its ability of migration and invasion. UNC119 promoted the progression of cell cycles and significantly induced HCC cell growth through the Wnt/β-catenin signaling pathway. In addition, UNC119 enhanced tumor migration and invasion through the TGF-β/epithelial-mesenchymal transition (EMT) pathway. The antibody against UNC119 (Anti- UNC119) efficiently inhibited the proliferation, migration and invasion of HCC cells by blocking the Wnt/β-catenin and TGF-β/EMT signaling pathways, respectively. Anti- UNC119 not only facilitated tumor remission, but also extended long-term survival of HCC-bearing mice.

CONCLUSION: UNC119 was significantly up-regulated in liver cancer cells and tissues. It promoted cell growth and migration through the Wnt/β-catenin and TGF-β/EMT signaling pathways, respectively. The anti-UNC119 treatment inhibited tumor cell proliferation, growth, migration and invasion by inhibiting the Wnt/β-catenin and GF-β/ EMT signaling pathways, respectively.