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mRNA and microRNA expression profiles of the NCI-60 integrated with drug activities
Hongfang Liu1, Petula D'Andrade, Stephanie Fulmer-Smentek
1Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Abstract:
As part of the Spotlight on Molecular Profiling series, we present here new profiling studies of mRNA and microRNA expression for the 60 cell lines of the National Cancer Institute (NCI) Developmental Therapeutics program (DTP) drug screen (NCI-60) using the 41,000-probe Agilent Whole Human Genome Oligo Microarray and the 15,000-feature Agilent Human microRNA Microarray V2. The expression levels of approximately 21,000 genes and 723 human microRNAs were measured. These profiling studies include quadruplicate technical replicates for six and eight cell lines for mRNA and microRNA, respectively, and duplicates for the remaining cell lines. The resulting data sets are freely available and searchable online in our CellMiner database. The result indicates high reproducibility for both platforms and an essential biological similarity across the various cell types. The mRNA and microRNA expression levels were integrated with our previously published 1,429-compound database of anticancer activity obtained from the NCI DTP drug screen. Large blocks of both mRNAs and microRNAs were identified with predominately unidirectional correlations to approximately 1,300 drugs, including 121 drugs with known mechanisms of action. The data sets presented here will facilitate the identification of groups of mRNAs, microRNAs, and drugs that potentially affect and interact with one another.
Insights
New molecular profiling of National Cancer Institute-60 (NCI-60) cell lines reveals correlations between gene and microRNA expression and anticancer drug activity. These findings aid in identifying potential drug-target interactions.
Area of Science:
- Cancer research
- Molecular biology
- Pharmacogenomics
Background:
- The National Cancer Institute's Developmental Therapeutics program (NCI DTP) drug screen utilizes the NCI-60 cell line panel for anticancer drug discovery.
- Understanding molecular profiles of these cell lines is crucial for interpreting drug activity and identifying mechanisms of action.
Purpose of the Study:
- To perform comprehensive mRNA and microRNA expression profiling of the NCI-60 cell lines.
- To integrate these molecular profiles with existing anticancer drug activity data.
- To identify correlations between gene/microRNA expression and drug responses.
Main Methods:
- Utilized Agilent Whole Human Genome Oligo Microarray (41,000 probes) for mRNA expression profiling.
- Employed Agilent Human microRNA Microarray V2 (15,000 features) for microRNA expression profiling.
- Integrated expression data with a database of 1,429 anticancer compounds and their activities from NCI DTP screens.
Main Results:
- Measured expression levels for approximately 21,000 genes and 723 human microRNAs across NCI-60 cell lines.
- Demonstrated high reproducibility for both mRNA and microRNA profiling platforms.
- Identified significant correlations between blocks of mRNAs/microRNAs and approximately 1,300 drugs, including 121 with known mechanisms.
Conclusions:
- The generated mRNA and microRNA expression datasets are publicly available via the CellMiner database.
- These comprehensive datasets facilitate the discovery of novel drug-target interactions and biomarkers.
- The study provides a valuable resource for understanding cellular responses to anticancer agents.
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