MicroRNA expression profiles for the NCI-60 cancer cell panel
MicroRNA expression profiles for the NCI-60 cancer cell panel
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DOI：
10.1158/1535-7163.mct-07-0009
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发表时间：
2007-05-01
影响因子：
5.7
通讯作者：
Sadee, Wolfgang
中科院分区：
文献类型：
--
作者：
Blower, Paul E.;Verducci, Joseph S.;Sadee, Wolfgang
了解癌细胞生物学和对药物治疗的反应的进步已受益于新的分子技术和整合来自多个来源信息的方法。 NCL-60是由60种不同人类癌细胞系组成的面板，已被国家癌症研究所使用，以筛选> 100,000种化合物和天然产物提取物进行抗癌活性。 NCL-60还针对mRNA和蛋白质表达，突变状态，染色体畸变和DNA拷贝数进行了介绍，生成了无与伦比的公共资源，用于综合化学基因组学研究。最近，已显示MicroRNA针对特定的mRNA集合，从而防止翻译或加速mRNA更新。为了补充现有的NCL-60数据集，我们测量了NCL-60中microRNA的表达水平，并将所得数据纳入CellMiner程序包中以进行集成分析。基于microRNA表达的细胞系组通常与组织类型以及基于mRNA表达的细胞系聚类一致。然而，与microRNA表达相比，mRNA表达在区分组织类型方面的信息更大。此外，我们发现MicroRNA表达模式与已知目标转录本的表达模式之间似乎没有显着相关性。 MicroRNA表达模式和复合效力模式的比较显示出显着的相关性，这表明microRNA可能在化学上发挥作用。与基因表达和其他生物学数据结合使用多元分析，microRNA表达谱可能为理解参与化学敏感和化学耐药的机制提供了关键的联系。
Advances in the understanding of cancer cell biology and response to drug treatment have benefited from new molecular technologies and methods for integrating information from multiple sources. The NCl-60, a panel of 60 diverse human cancer cell lines, has been used by the National Cancer Institute to screen > 100,000 chemical compounds and natural product extracts for anticancer activity. The NCl-60 has also been profiled for mRNA and protein expression, mutational status, chromosomal aberrations, and DNA copy number, generating an unparalleled public resource for integrated chemogenomic studies. Recently, microRNAs have been shown to target particular sets of mRNAs, thereby preventing translation or accelerating mRNA turnover. To complement the existing NCl-60 data sets, we have measured expression levels of microRNAs in the NCl-60 and incorporated the resulting data into the CellMiner program package for integrative analysis. Cell line groupings based on microRNA expression were generally consistent with tissue type and with cell line clustering based on mRNA expression. However, mRNA expression seemed to be somewhat more informative for discriminating among tissue types than was microRNA expression. In addition, we found that there does not seem to be a significant correlation between microRNA expression patterns and those of known target transcripts. Comparison of microRNA expression patterns and compound potency patterns showed significant correlations, suggesting that microRNAs may play a role in chemoresistance. Combined with gene expression and other biological data using multivariate analysis, microRNA expression profiles may provide a critical link for understanding mechanisms involved in chemosensitivity and chemoresistance.