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Mar 15, 2010 (Vol. 30, No. 6)

miRNAs' Therapeutic Potential

Scientists Scrutinize Promising Molecules as Potential Drug Targets and Biomarkers

  • Cancer Cell Profiling

    Stephanie Fulmer-Smentek, Ph.D., R&D group manager for biological systems at Agilent Technologies, has been working with the National Cancer Institute (NCI) to characterize miRNA and mRNAs for the NCI-60, a set of cancerous cell lines derived from nine different tissues. Dr. Fulmer-Smentek will present new miRNA and mRNA profiling data obtained using Agilent’s gene-expression and miRNA microarray platforms, providing what she and her team hopes will be a model system for such analyses.

    Dr. Fulmer-Smentek and her group worked with isolated total RNAs from the NCI-60, performing hybridization assays using whole-genome expression arrays to detect mRNA expression, they then analyzed the samples for miRNA using the company’s miRNA microarray. This approach allowed comparison between gene-expression profiles and miRNA profiles, and they reported that the data demonstrated high producibility across replicates for both platforms.

    The researchers found a strong correlation between the two profiles and the tumor cell tissue of origin. But, Dr. Fulmer-Smentek adds, “we found that the diversity within and between tissues of origin is much greater for miRNA than mRNA. This data might be useful in terms of providing a framework to which other data can be compared. But, whether data from the NCI-60 will allow definitive identification of the tissue of origin for other samples remains to be seen. There is, however, strong evidence in the field that miRNA profiles can be used to define the tissue of origin for cancer samples.

    “In connecting the mRNA data with the miRNA we do find evidence of some of the same interactions in terms of genes that are known to be related to deletion-specific miRNAs, for example, the miRNA17-92 cluster on chromosome 13.” This suggests that the NCI-60 can indeed serve a role in helping to define interactions between different miRNA and their mRNA targets.

    “One of the interesting things we found was that, in general, for many different tissues, there is a strong correlation between cell lines for both the miRNA and mRNA profiles, but the level of correlation is quite different for different tissues of origin.” For example, she found that the leukemia cell lines were quite distinct from the other cancer cell lines according to their miRNA and mRNA profiles, but show “a lot of diversity within the group.”

    The data that was developed during these studies “provides a huge wealth of information for researchers,” says Dr. Fulmer-Smentek. “It extends the present knowledge of the cell lines, and allows for more extensive analysis, not just within these two new datasets, but also with all of the other available biological data about these cell lines and extending to other similar types of data on other cancer samples.” The take-home point is that there is a tremendous “opportunity to extend the analysis to many other types of data, putting miRNA and mRNA in context of the larger biological picture.”

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