Blower Paul E, Verducci Joseph S, Lin Shili, Zhou Jin, Chung Ji-Hyun, Dai Zunyan, Liu Chang-Gong, Reinhold William, Lorenzi Philip L, Kaldjian Eric P, Croce Carlo M, Weinstein John N, Sadee Wolfgang
Program of Pharmacogenomics, Department of Pharmacology and the Comprehensive Cancer Center, College of Medicine, The Ohio State University, 5072 Graves Hall, 333 West 10th Avenue, Columbus, OH 43210, USA.
Mol Cancer Ther. 2007 May;6(5):1483-91. doi: 10.1158/1535-7163.MCT-07-0009. Epub 2007 May 4.
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 NCI-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 NCI-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 NCI-60 data sets, we have measured expression levels of microRNAs in the NCI-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.
对癌细胞生物学和药物治疗反应的理解取得的进展得益于新的分子技术以及整合来自多个来源信息的方法。美国国立癌症研究所使用了由60种不同人类癌细胞系组成的NCI - 60来筛选超过100,000种化合物和天然产物提取物的抗癌活性。NCI - 60还进行了mRNA和蛋白质表达、突变状态、染色体畸变以及DNA拷贝数的分析，为综合化学基因组学研究生成了无与伦比的公共资源。最近，已证明微小RNA靶向特定的mRNA组，从而阻止翻译或加速mRNA周转。为补充现有的NCI - 60数据集，我们测量了NCI - 60中微小RNA的表达水平，并将所得数据纳入CellMiner程序包进行综合分析。基于微小RNA表达的细胞系分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，mRNA表达在区分组织类型方面似乎比微小RNA表达更具信息性。此外，我们发现微小RNA表达模式与已知靶转录本的表达模式之间似乎没有显著相关性。微小RNA表达模式与化合物效力模式的比较显示出显著相关性，表明微小RNA可能在化学抗性中起作用。通过多变量分析将微小RNA表达谱与基因表达及其他生物学数据相结合，可能为理解化学敏感性和化学抗性所涉及的机制提供关键联系。
