5′-Triphosphate-siRNA against survivin gene induces interferon production and inhibits proliferation of lung cancer cells in vitro

Kai Wang, Xiaojuan Chen, Fei Yan, Yaling Xing, Xingxing Yang, Jian Tu, Zhongbin Chen*

*Corresponding author for this work

    Research output: Contribution to journalArticle

    9 Citations (Scopus)

    Abstract

    Survivin is a new member of the inhibitors of apoptosis family and upregulated in various human malignancies including human lung cancer. In this study, we proposed a new strategy for RNA interference (RNAi)-mediated anticancer therapy combining activation of interferon production with RNAi using 5′-triphosphate-siRNA (3p-siRNA) against survivin gene. We designed and generated 3p-siRNA targeting human survivin gene (3p-survivin-siRNA). The findings reported here demonstrated that 3p-survivin-siRNA induced a 3p-dependent type-I interferon response when transfected into human lung cancer cells. The 3p-survivin-siRNA significantly inhibited lung cancer cell proliferation in a 3p-dependent manner. The anticancer effect of 3p-survivin-siRNA was superior to that of conventional siRNA. The expression level of survivin in 3p-survivin-siRNA-treated A549 cells was significantly lower than that of siRNA. Furthermore, when 3p-survivin-siRNA silencing approach was combined with radiation treatment, 3p-survivin-siRNA increases the cytotoxicity of A549 cells and induces more cells to undergo apoptosis. In conclusion, our results suggest that 3p-survivin-siRNA could act as a powerful bifunctional molecule with potential for developing promising radiosensitization therapeutics against human lung cancer.

    Original languageEnglish
    Pages (from-to)294-304
    Number of pages11
    JournalJournal of Immunotherapy
    Volume36
    Issue number5
    DOIs
    Publication statusPublished - Jun 2013

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    Keywords

    • 50-triphosphated sirna
    • Ifn-a/b
    • Lung cancer cell
    • Rnai
    • Survivin

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