Purpose: UNC119 was reported to be significantly up-regulated in hepatic cancer cells. However, the clinical significance of target UNC119 to reduce UNC119 expression and mechanisms in hepatocellular carcinoma (HCC) are not well understood. Our purpose was to study how UNC119 is expressed in HCC and its connection with HCC progression.
Methods: UNC119 expression was assessed with quantitative real-time PCR (qRT-PCR), western blot and immunohistochemical analyses in HCC cell lines and in tissues. The biological function of UNC119 for proliferation, growth and cell cycle of tumor cells were also analyzed both in vitro and in vivo.
Results: UNC119 expression was up-regulated both in HCC cell lines as well as in tissues through comparison with normal liver cells and tissues. Higher concentration level of UNC119 not only promoted proliferation, but also enhanced migration and invasion of HCC cells. UNC119 promoted the progression of cell cycle and significantly promoted HCC cells growth through Wnt/β-catenin signal pathway and enhanced tumor migration and invasion via TGF-β/epithelial-mesenchymal transition (EMT) pathway. Antibody for UNC119 (Anti-UNC119) efficiently inhibited HCC cells proliferation, migration and invasion by blocking Wnt/β-catenin and TGF-β/EMT signal pathway, respectively. Anti-UNC119 was not only beneficial for tumor remission, but also contributed to long-term survival of HCC-bearing mice.
Conclusion: UNC119 is significantly up-regulated and promoted cell growth and migration in hepatic cancer cells and tissues via Wnt/β-catenin signal pathway and TGF-β/EMT signal pathway, respectively. Anti-UNC119 treatment inhibited cell proliferation, growth, migration and invasion through inhibition of Wnt/β-catenin and GF-β/EMT signal pathway, respectively.