Citation:

Harrill, A., S. McCullough, C. Wood, J. Kahle, AND B. Chorley. MicroRNA Biomarkers of Toxicity in Biological Matrices. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 152(2):264-272, (2016).

Impact/Purpose:

MicroRNAs (miRNAs) are small, non-coding RNA species that selectively bind mRNA molecules and alter their expression. MiRNA expression is responsive to acute environmental cues, often exhibiting alterations prior to more overt pathophysiological changes, and these miRNA can appear in different biological matrices. In some cases, these alterations have been linked to specific cellular responses, including death, proliferation, metabolism, and inflammation. Many studies have therefore studied miRNAs as promising biomarkers for toxicology. Thus, there is potential to exploit miRNAs as toxicological biomarkers of xenobiotic exposure and exposure-induced adverse health effects. However, there are important technical challenges and knowledge gaps that need to be addressed before miRNAs can be widely applied in hazard identification and safety assessment. In this review, we describe several of these challenges and discuss recently identified miRNA biomarkers of toxicity. Our goals are to provide an overview of miRNA features in biofluids, highlight current miRNA markers of tissue-specific toxicity and injury, and discuss future applications. These biomarkers have immediate relevance in the Adverse Outcome Pathway development of many ongoing projects, including cancer and liver steatosis AOPs. They have utility to link to key events within the AOP network and identify tissue perturbations that may lead to an adverse outcome of interest; to be able to measure these biomarkers in accessible matrices, such as blood, further increases the utility in multiple studies.

Description:

Biomarker measurements that reliably correlate with tissue injury and can be measured from sampling accessible biofluids offer enormous benefits in terms of cost, time, and convenience when assessing environmental and drug-induced toxicity in model systems or human cohorts. MicroRNAs (miRNAs) have emerged in recent years as a promising new type of biomarker for monitoring toxicity. Recent enthusiasm for miRNA biomarker research has been fueled by discoveries that certain miRNA species are cell-type specific and released during injury, thus raising the possibility of using biofluid-based miRNAs as a “liquid biopsy” that may be obtained by sampling extracellular fluids. As biomarkers, miRNAs demonstrate improved stability as compared to many protein markers and sequences are largely conserved across species, simplifying analytical techniques. Recent efforts have sought to identify miRNAs that are released into accessible biofluids following xenobiotic exposure, using compounds that target specific organs. While still early in the discovery phase, miRNA biomarkers will have an increasingly important role in the assessment of adverse effects of both environmental chemicals and pharmaceutical drugs. Here, we review the current findings of biofluid-based miRNAs, as well as highlight technical challenges in assessing toxicologic pathology using these biomarkers.

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