Inhibition of WWP2 suppresses proliferation, and induces G1 cell cycle arrest and apoptosis in liver cancer cells

Primary liver cancer is one of the most common and aggressive human malignancies worldwide. As numerous studies have revealed that WW domain containing E3 Ub-protein ligase 2 (WWP2) exerts cancer-specific functions, the present study assessed the role of WWP2 in liver cancer. WWP2 was revealed to be significantly overexpressed in liver cancer tissues compared with paired normal tissues at the mRNA as well as at the protein level. Furthermore, small interfering RNA-mediated WWP2 knockdown in liver cancer cell lines was demonstrated to inhibit cell proliferation, cause cell cycle arrested in G1 phase and to induce apoptosis as revealed by a Cell Counting Kit-8 assay and flow cytometric analysis. In addition, western blot analysis revealed that WWP2 knockdown significantly increased the expression of apoptosis-associated markers caspase-7, caspase-8 and B-cell lymphoma 2 (Bcl-2)-associated X in liver cancer cell lines, while Bcl-2 was significantly decreased. In conclusion, the present study suggested that WWP2 may exert important functions in the over-proliferation and evasion of apoptosis of liver cancer, likely through regulating the expression of apoptosis-associated markers. Furthermore, WWP2 may represent a novel diagnostic marker and molecular therapeutic target for liver cancer.