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HERO ID
3997218
Reference Type
Journal Article
Title
5'-triphosphate-siRNA against survivin gene induces interferon production and inhibits proliferation of lung cancer cells in vitro
Author(s)
Wang, K; Chen, X; Yan, F; Xing, Y; Yang, X; Tu, J; Chen, Z
Year
2013
Is Peer Reviewed?
Yes
Journal
Journal of Immunotherapy
ISSN:
1524-9557
EISSN:
1537-4513
Volume
36
Issue
5
Page Numbers
294-304
Language
English
PMID
23719240
DOI
10.1097/CJI.0b013e318294183b
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.
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