Silencing of survivin expression leads to reduced proliferation and cell cycle arrest in cancer cells

Yuhuan Li, Da Liu, Yulin Zhou, Yujing Li, Jing-JIng Xie, Robert J. Lee, Yong Cai, Lesheng Teng

Research output: Contribution to journalArticleResearchpeer-review

38 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1187-1194
Number of pages8
JournalJournal of Cancer
Volume6
Issue number11
DOIs
Publication statusPublished - 2015
Externally publishedYes

Keywords

  • Apoptosis
  • Cancer
  • Cell cycle checkpoint
  • RNA interference
  • Survivin

Cite this