Inhibition of S-phase kinase-associated protein 2-mediated p27 degradation suppresses tumorigenesis and the progression of hepatocellular carcinoma.

Abstract In order to determine the protein expression of S‑phase kinase‑associated protein 2 (Skp2) and p27kip1, and to evaluate their possible prognostic values in malignant liver cancer, tissue samples from 50 patients and 40 controls were assessed and analyzed by immunohistochemistry and western blot analysis. Positive expression of Skp2 was observed in 35 (70.0%) of the hepatocellular carcinoma samples; however, the positive expression of p27kip1 was observed in 6 (15.0%) of the hepatocellular carcinoma samples. The expression of Skp2 was significantly negatively correlated with the expression of p27 (P<0.01). The results from Annexin V‑propidium iodide staining and MTT assays indicated that interference of Skp2 significantly induced apoptosis and inhibited the proliferation of SSMC‑7721 cells. In addition, the levels of endogenous p27 increased in the HepG2 and SSMC‑7721 cells following transfection with siRNA specific to Skp2, suggesting that the Skp2‑mediated degradation of p27kip1 was important in the proliferation of tumor cells. The present study, therefore, provided a molecular reference for the treatment of liver cancer.