Reporter assay, cell proliferation assay, and xenotransplantation experiments were used to show the functional consequence and importance of Pin1-HBx interaction in hepatocarcinogenesis.
To further validate the role of PIN1 in hepatocarcinogenesis, PIN was suppressed by RNA interference (siRNA) in the HCC cell line PLC/PRF/5. siRNA-PIN1 transfection of PLC/PRF/5 cells led to repression of PIN1 expression, resulting in decreased levels of beta-catenin and cyclin D1. siRNA-PIN1 transfectants showed lower cell proliferation rates, reduced colony formation, and retarded cell cycle progression, with an increase in cells residing in G0/G1.
These results showed that PIN1 overexpression leading to beta-catenin accumulation might be a critical event in hepatocarcinogenesis, and that PIN1 is a potential target for therapeutic intervention in HCC.