title: 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.
authors.affiliation: Department of Digestive System, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Qi
authors.affiliation: Department of Transfusion Center, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Digestive System, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Digestive System, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China.
authors.forename: Peixin
authors.initials: P
authors.lastname: Hu
authors.affiliation: Department of Hematology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China.
authors.forename: Tan
authors.initials: T
authors.lastname: Sang
mesh_terms: D017209:Apoptosis; D063646:Carcinogenesis / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D021381:Protein Transport; D034622:RNA Interference; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D044786:S-Phase Kinase-Associated Proteins; D025801:Ubiquitin; D050760:Cyclin-Dependent Kinase Inhibitor p27; D046988:Proteasome Endopeptidase Complex