title: 5'-triphosphate-siRNA against survivin gene induces interferon production and inhibits proliferation of lung cancer cells in vitro.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui Province, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Chen
authors.forename: Fei
authors.initials: F
authors.lastname: Yan
authors.forename: Yaling
authors.initials: Y
authors.lastname: Xing
authors.forename: Xingxing
authors.initials: X
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Tu
authors.forename: Zhongbin
authors.initials: Z
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002277:Carcinoma / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D048708:Cell Growth Processes / Q000235:genetics; D059248:Chemoradiotherapy; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D016899:Interferon-beta / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D011122:Polyphosphates / Q000737:chemistry; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics; D011827:Radiation; D011838:Radiation-Sensitizing Agents; D011971:Receptors, Immunologic; D000077022:Survivin; D019076:Transgenes / Q000235:genetics
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D011122:Polyphosphates; D034741:RNA, Small Interfering; D011838:Radiation-Sensitizing Agents; D011971:Receptors, Immunologic; D000077022:Survivin; D016899:Interferon-beta; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; C005692:triphosphoric acid