J Cancer 2015; 6(11):1187-1194. doi:10.7150/jca.12437
Silencing of Survivin Expression Leads to Reduced Proliferation and Cell Cycle Arrest in Cancer Cells
1. Institute of Life Sciences, Jilin University, Changchun, Jilin, P. R. China
2. Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A
Li Y, Liu D, Zhou Y, Li Y, Xie J, Lee RJ, Cai Y, Teng L. Silencing of Survivin Expression Leads to Reduced Proliferation and Cell Cycle Arrest in Cancer Cells. J Cancer 2015; 6(11):1187-1194. doi:10.7150/jca.12437. Available from http://www.jcancer.org/v06p1187.htm
Survivin is an anti-apoptotic gene that is overexpressed in most human tumors. RNA interference using short interfering RNA (siRNA) can be used to specifically inhibit survivin expression. Tumor cells were treated with a newly designed survivin siRNA, which was modified with 2′-OMe. Cellular survivin mRNA and protein levels were determined by real-time qRT-PCR and Western blot, respectively. Cell cycle and apoptosis were determined by flow cytometry. Cell proliferation was measured by MTT assay. Our data showed that the novel survivin-targeted siRNA could efficiently knockdown the expression of survivin and inhibit cell proliferation. Survivin mRNA was reduced by 95% after 48h treatment with 20nM siRNA. In addition, the siRNA could markedly arrest the cell cycle at the G2/M checkpoint and induce cellular apoptosis in a dose-dependent manner. The percentage of apoptotic cells reached 50% when treated with 40nM siRNA. In conclusion, we have identified a novel chemically modified siRNA against survivin that is highly efficient and delineated its mechanism of action, thus demonstrating a potential therapeutic role for this molecule in cancer. Further evaluation of this siRNA for therapeutic activity is warranted.
Keywords: survivin, RNA interference, cancer, apoptosis, cell cycle checkpoint