Epigenetic silencing of IRF7 and/or IRF5 in lung cancer cells leads to increased sensitivity to oncolytic viruses.
Epigenetic silencing of IRF7 and/or IRF5 in lung cancer cells leads to increased sensitivity to oncolytic viruses.
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DOI：
10.1371/journal.pone.0028683
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Tainsky MA
中科院分区：
文献类型：
--
作者：
Li Q;Tainsky MA
缺陷的IFN信号传导导致先天免疫的丧失，并且在水疱性口炎病毒（VSV）感染后使细胞对增强的溶细胞杀伤敏感。对正常人支气管上皮细胞Beas 2B和7肺癌细胞的先天免疫状态的检查揭示，癌细胞中IFN信号传导的消除与对VSV感染的更高敏感性相关。肺癌细胞系和原发性肿瘤组织中IFN途径的破坏是由关键干扰素应答性转录因子IRF 7和/或IRF 5的表观遗传沉默引起的。尽管5-氮杂-2 ′-脱氧胞苷处理不能重新激活IRF 7和IRF 5表达或保护细胞免受VSV感染，但通过改变IRF表达来操纵IFN信号传导改变了这些细胞的病毒易感性。使用IRF 5 + IRF 7过表达可以部分保护肺癌细胞免受病毒杀伤，而通过将siRNA转染至IRF 5 + IRF 7而破坏IFN途径增加了细胞对病毒感染的脆弱性。因此，IRF 5和IRF 7是决定肺癌细胞病毒敏感性的IFN途径中的关键转录因子;肺癌组织中表观遗传学受损的IFN途径为溶瘤病毒治疗成功选择性杀死癌细胞提供了潜在的生物标志物。
Defective IFN signaling results in loss of innate immunity and sensitizes cells to enhanced cytolytic killing after Vesticular Stomatitis Virus (VSV) infection. Examination of the innate immunity status of normal human bronchial epithelial cells Beas2B and 7 lung cancer cells revealed that the abrogation of IFN signaling in cancer cells is associated with greater sensitivity to VSV infection. The disruption of the IFN pathway in lung cancer cell lines and primary tumor tissues is caused by epigenetic silencing of critical interferon responsive transcription factors IRF7 and/or IRF5. Although 5-aza-2′-deoxycytidine treatment fails to reactivate IRF7 and IRF5 expression or protect cells from VSV infection, manipulating IFN signaling by altering IRF expression changes the viral susceptibility of these cells. Lung cancer cells can be partially protected from viral killing using IRF5+IRF7 overexpression, whereas IFN pathway disruption by transfection of siRNAs to IRF5+IRF7 increases cells' vulnerability to viral infection. Therefore, IRF5 and IRF7 are key transcription factors in IFN pathway that determine viral sensitivity of lung cancer cells; the epigenetically impaired IFN pathway in lung cancer tissues provides potential biomarkers for successful selective killing of cancer cells by oncolytic viral therapy.
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影响因子：
2.9
作者：
KE, Y;REDDEL, RR;HARRIS, CC
通讯作者：
HARRIS, CC
DOI：
10.1165/rcmb.2009-0254oc
发表时间：
2010-09-01
影响因子：
6.4
作者：
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通讯作者：
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影响因子：
2.3
作者：
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通讯作者：
Seif, I
影响因子：
6.4
作者：
Muster, T;Rajtarova, J;Bergmann, M
通讯作者：
Bergmann, M
影响因子：
5.4
作者：
Balachandran, S;Porosnicu, M;Barber, GN
通讯作者：
Barber, GN