Circulating microRNAs: non-invasive tissue- and mechanism-specific biomarkers for in-vitro diagnostics and drug development
MicroRNAs (miRNAs) are small non-coding RNAs that are highly conserved across mammalian species. They regulate gene activity and are considered valuable biomarkers, because 1) all cell types dispose of a unique miRNA expression pattern that is required to maintain cell function, but modified during onset and development of disease; 2) active or passive release of miRNAs from cells enables minimal- or non-invasive detection in cell-free biofluids including serum, plasma, urine, and cerebrospinal fluid (CSF); 3) quantitative assays such as next-generation sequencing or RT-qPCR are available to discover and validate miRNA biomarkers in cell-free biofluids at high throughput and relatively low cost. This talk will initially highlight the importance of standardization of microRNA analysis by RT-qPCR and NGS in extracellular vesicles as well as total microRNA extracts from liquid biopsies, since pre-analytical as well as analytical variability can severely hamper the reproducibility of microRNA results. On the basis of a case study (hepatomiR), our approach at TAmiRNA to discovering microRNA biomarkers by NGS, and demonstrating their clinical utility for prognosis of post-operative liver failure will be presented. Finally, data regarding the application of circulating microRNAs as safety biomarkers in toxicology and drug development will be discussed.