RNAi-mediated silencing of the Skp-2 gene causes inhibition of growth and induction of apoptosis in human renal carcinoma cells.

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.