Читать книгу Genomic and Epigenomic Biomarkers of Toxicology and Disease - Группа авторов - Страница 30

The identification of miRNA biomarkers that can distinguish the biological effects of toxicant and other environmental chemical exposures is a much needed tool for toxicological and regulatory science. Studies have suggested that these biomarkers, which are stable and present in most biofluids, may indicate general toxicity in a tissue-specific manner. Further, the RNA content of EVs may reflect the type and the physiological or pathological state of the source cells. Extracellular vesicle-mediated functional transfer of miRNAs to recipient cells has been demonstrated both in vitro and in vivo for a variety of diseases and physiological states, but the mechanisms by which EVs are selectively packaged and “addressed” to different cell types are still largely unknown. In addition to specificity of tissue and MOA, in vitro and in vivo studies suggest early, dose-responsive alterations in expression that can indicate breaking points that may lead to adverse health outcomes. Recent development of miRNA biomarkers in biofluids for clinical indications provide promise that similar uses can be leveraged in toxicological sciences. Despite these qualities, there remain significant technical challenges to reducing variability in measurements and to increasing our confidence in the application of these biomarkers. A standardization of protocols and reporting efforts analogous to the Transcriptomics Reporting Framework (Gant et al. 2017), and large-scale database efforts to categorize EV contents relating to source cells will be important for biomarker identification and for linking biofluid measured miRNAs to specific tissues, cells, and biological effects (see exRNA Atlas: Murillo et al. 2019). These and other concerted efforts will ultimately lead to a consistent and widespread use of miRNAs in regulatory and toxicological sciences.