Expressed gene clusters associated with cellular sensitivity and resistance towards anti-viral and anti-proliferative actions of interferon
Expressed gene clusters associated with cellular sensitivity and resistance towards anti-viral and anti-proliferative actions of interferon
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DOI：
10.1016/j.jmb.2004.07.065
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发表时间：
2004-09-17
影响因子：
5.6
通讯作者：
Williams, BRG
中科院分区：
文献类型：
--
作者：
Khabar, KSA;al-Haj, L;Williams, BRG
干扰素（IFN）是诱导大量基因的多功能蛋白，这些基因介导许多生物学过程，包括宿主防御，细胞生长控制，信号传导和代谢。对IFN刺激基因（ISG）的3'-非翻译区域的生物信息学分析表明，IFN诱导的mRNA的大约10％存在于IFN诱导的大约10％。人类上皮细胞系，愿望和293，以及人类B细胞系，Daudi和RPMI 1788，评估了它们对I型IFN的反应。由于它们对IFN-Alpha的抗病毒和抗增殖作用的反应不同，因此它们被用作基因组宽为基因表达的细胞模型。 IFN-Alpha的抗病毒和抗增殖作用分别比293和RPMI 1788细胞更有效，而Daudi细胞则更有效。这些结果与通过监测STAT1介导的IFN诱导6-16 mRNA的表达评估的STAT1驱动基因表达相关。干扰素能够诱导很大一部分的常见和不同的is-ey-genes，但是表达模式是不同的，并且取决于细胞的类型，IFN的类型以及细胞对IFN的敏感性的状态。聚类算法产生了两个信息表达的基因簇，它们与IFN的抗病毒和抗增殖作用有选择性地相关。在IFN生物学中使用合理设计的微阵列实验产生了信息簇，这些群集可能提供候选基因诊断或评估治疗可能性。 （c）2004 Elsevier Ltd.保留所有权利。
Interferons (IFN) are multi-functional proteins that induce a large number of genes which mediate many biological processes including host defense, cell growth control, signaling, and metabolism. Bioinformatics analysis of the 3'-untranslated regions of IFN-stimulated genes (ISGs) showed that the AU-rich elements (ARE) exist in approximately 10% of the mRNA induced by IFN. The human epithelial cell lines, WISH and 293, and the human B cell lines, Daudi and RPMI 1788, were assessed for their response to type-I IFN. Due to their differential response to the anti-viral and anti-proliferative action of IFN-alpha, they were used as cellular models for genome wide ARE-gene expression. The anti-viral and anti-proliferative actions of IFN-alpha were substantially more potent against WISH and Daudi cells than 293 and RPMI 1788 cells, respectively. These results correlated with the Stat1-driven gene expression as assessed by monitoring the expression of Stat1-mediated IFN-inducible 6-16 mRNA. Interferons were able to induce a significant proportion of common and distinct ARE-genes, but the patterns of expression were different and dependent on the type of the cell, type of IFN, and status of the cellular sensitivity to IFN. Clustering algorithms generated two informative expressed gene clusters that were selectively associated with cellular sensitivity and resistance to the antiviral and anti-proliferative action of IFN. Use of rationally designed microarray experiments in IFN biology yielded informative clusters that may provide candidate genes for diagnostic or for evaluation of therapeutic possibilities. (C) 2004 Elsevier Ltd. All rights reserved.