Urine microRNA profiling to discover biomarkers for nephrotoxicity

microRNAs represent the best described class of small RNAs (21-23nt) and have been shown to function as post-transcriptional regulators of gene expression. The high relative stability of microRNA in common clinical samples such as serum/plasma, urine and other biofluids, and the ability of micro RNA expression profiles to accurately classify discrete tissue types and specific disease states have positioned microRNA quantification as a promising new biomarker for a wide range of diagnostic applications. We have developed a genome-wide LNATM-based microRNA qPCR platform with unparalleled sensitivity and robustness. A single cDNA synthesis reaction is sufficient for full microRNA analysis without the need for preamplification. The platform is thus highly suited to high-throughput microRNA profiling from challenging clinical source material. Thousands of biofluid samples, including blood derived serum/plasma and urine, have been profiled in-house allowing the development of focused microRNA assay sets for the discovery of micro RNA biomarkers for disease, toxicology and injury studies. Here we demonstrate the applicability of urine microRNA profiling for the discovery of potential biomakers for nephrotoxin induced kidney injury using the Toxicology Focus micro RNA PCR Panel. We also present our approach to the challenging aspect of data processing and normalization specifically for microRNA profiling in urine. Urine microRNA profiling to discover biomarkers for nephrotoxicity Jörg Krummheuer, Thorarinn Blondal, Ditte Andreasen, Maria Wrang Teilum, Kim Bundvig Barken, Niels Tolstrup, Nana Jacobsen, Ina K Dahlsveen and Peter Mouritzen Exiqon A/S, Skelstedet 16, 2950 Denmark