title: Silencing of Survivin Expression Leads to Reduced Proliferation and Cell Cycle Arrest in Cancer Cells.
abstract: 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.
authors.affiliation: 1. Institute of Life Sciences, Jilin University, Changchun, Jilin, P. R. China.
authors.forename: Yuhuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: 1. Institute of Life Sciences, Jilin University, Changchun, Jilin, P. R. China.
authors.forename: Da
authors.initials: D
authors.lastname: Liu
authors.affiliation: 1. Institute of Life Sciences, Jilin University, Changchun, Jilin, P. R. China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: 1. Institute of Life Sciences, Jilin University, Changchun, Jilin, P. R. China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Li
authors.affiliation: 1. Institute of Life Sciences, Jilin University, Changchun, Jilin, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: 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.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
authors.affiliation: 1. Institute of Life Sciences, Jilin University, Changchun, Jilin, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cai
authors.affiliation: 1. Institute of Life Sciences, Jilin University, Changchun, Jilin, P. R. China.
authors.forename: Lesheng
authors.initials: L
authors.lastname: Teng
keywords: RNA interference; apoptosis; cancer; cell cycle checkpoint; survivin