基因沉默
RNA干扰
生物
小干扰RNA
细胞凋亡
基因表达
癌症研究
基因
癌细胞
细胞生物学
癌症
转染
核糖核酸
遗传学
作者
Irena Crnković‐Mertens,Felix Hoppe‐Seyler,Karin Butz
出处
期刊:Oncogene
[Springer Nature]
日期:2003-11-13
卷期号:22 (51): 8330-8336
被引量:98
标识
DOI:10.1038/sj.onc.1206973
摘要
Increased resistance to apoptosis is a hallmark of many tumor cells. The functional inhibition of specific antiapoptotic factors may provide a rational basis for the development of novel therapeutic strategies. We investigated here whether the RNA interference (RNAi) technology could be used to increase the apoptotic susceptibility of cancer cells. As a molecular target, we chose the antiapoptotic livin (ML-IAP, KIAP) gene, which is expressed in a subset of human tumors. We identified vector-borne small interfering (si)RNAs, which could efficiently block endogenous livin gene expression. Silencing of livin was associated with caspase-3 activation and a strongly increased apoptotic rate in response to different proapoptotic stimuli, such as doxorubicin, UV-irradiation, or TNFα. The effects were specific for Livin-expressing tumor cells. Our results (i) provide direct evidence that the intracellular interference with livin gene expression resensitizes human tumor cells to apoptosis, (ii) define the livin gene as a promising molecular target for therapeutic inhibition, and (iii) show that the livin gene is susceptible to efficient and specific silencing by the siRNA technology.
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