Abstract
MicroRNAs (miRNA) are a group of short noncoding RNAs that regulate gene expression at the posttranscriptional level. They are involved in many biological processes, including development, differentiation, apoptosis, and carcinogenesis. Because miRNAs may play a role in the initiation and progression of cancer, they comprise a novel class of promising diagnostic and prognostic molecular markers and potential drug targets. By applying an LNA-enhanced microarray platform, we studied the expression profiles of 955 miRNAs in the NCI-60 cancer cell lines and identified tissue- and cell-type-specific miRNA patterns by unsupervised hierarchical clustering and statistical analysis. A comparison of our data to three previously published miRNA expression studies on the NCI-60 panel showed a remarkably high correlation between the different technical platforms. In addition, the current work contributes expression data for 369 miRNAs that have not previously been profiled. Finally, by matching drug sensitivity data for the NCI-60 cells to their miRNA expression profiles, we found numerous drug-miRNAs pairs, for which the miRNA expression and drug sensitivity profiles were highly correlated and thus represent potential candidates for further investigation of drug resistance and sensitivity mechanisms.
Highlights
Twenty years have passed since the NCI-60 cell panel for anticancer drug screening was established in 1990 [1], and today, these cell lines represent the most extensively studied and best characterized set of tumor cells available
The panel comprises 59 human cancer cell lines derived from 9 different tissues of origin: melanoma, leukemia, breast, central nervous system (CNS), colon, lung, ovary, prostate, and kidney. [One breast cancer cell line, MB-468, has high identity to MDA-MB-231 and was excluded from the NCI-60 panel that we received for our analysis.] Chemosensitivity profiles of the NCI-60 cells for more than 100,000 compounds have been generated, and together with genomic, transcriptomic, proteomic, epigenomic, and metabolomic data, this information is publicly available via the NCI Developmental Therapeutics Pro
We present here a comprehensive analysis of the NCI-60 cell line panel miRNA landscape, where the expression of 955 miRNAs has been correlated to drug sensitivity, mRNA and protein level, and tissue of origin www.aacrjournals.org of the cells
Summary
Twenty years have passed since the NCI-60 cell panel for anticancer drug screening was established in 1990 [1], and today, these cell lines represent the most extensively studied and best characterized set of tumor cells available. MiRNAs constitute a group of short, noncoding RNAs which repress gene expression at the posttranscriptional level by binding to complementary sequences in the 30-untranslated region of their target mRNAs [7]. They are involved in the regulation of numerous biological processes, including differentiation, proliferation, and apoptosis. We present here a comprehensive analysis of the NCI-60 cell line panel miRNA landscape, where the expression of 955 miRNAs has been correlated to drug sensitivity, mRNA and protein level, and tissue of origin www.aacrjournals.org. Our analysis is limited to the 365 miRNAs reported to be expressed in at least 10% of the cell lines by Liu and colleagues.)
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