title: RNAi-mediated silencing of the Skp-2 gene causes inhibition of growth and induction of apoptosis in human renal carcinoma cells.
abstract: Renal cancer ranks one of the most frequent causes of cancer death in the world. S-phase kinase-associated protein 2 (SKP 2) is overexpressed in human tumors and has prognostic value in many cancers including renal cancer, indicating its potential as a therapeutic target. In this study, we investigated the therapeutic potential of Skp-2 in renal cancer using the technique of RNA silencing via short hairpin RNA (shRNA). Synthetic shRNA duplexes against Skp-2 were introduced to down-regulate the expression of Skp-2 in a highly malignant renal carcinoma cell line, ACHN. The results indicated that siRNA targeting of Skp-2 could lead to an efficient and specific inhibition of endogenous Skp-2 activity. Furthermore, we found that depletion of Skp-2 caused a dramatic cell cycle arrest, followed by massive apoptotic cell death, and eventually resulted in a significant decrease in growth, viability and tumor formation in renal cancer cell lines studied.
authors.affiliation: Department of Pathology, Taizhou Central Hospital of Taizhou Enze Medical Group Taizhou, China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Pathology, Taizhou Hospital of Taizhou Enze Medical Group Linhai, China.
authors.forename: Meifu
authors.initials: M
authors.lastname: Gan
authors.affiliation: Department of Pathology, Taizhou Central Hospital of Taizhou Enze Medical Group Taizhou, China.
authors.forename: Xuequan
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Pathology, Taizhou Central Hospital of Taizhou Enze Medical Group Taizhou, China.
authors.forename: Lanxi
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pathology, Taizhou Central Hospital of Taizhou Enze Medical Group Taizhou, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, Taizhou Central Hospital of Taizhou Enze Medical Group Taizhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D006801:Humans; D015151:Immunoblotting; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics*; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; D044786:S-Phase Kinase-Associated Proteins
keywords: RNA silencing; Renal carcinoma; Skp-2; apoptosis; cell cycle