Citation:

Hines, R. AND B. Chorley. Application of miRNAs as Biomarkers of Exposure and Effects in Risk Evaluation. Environmental Mutagen and Genomics Society Annual Meeting, Kansas City, MO, September 24 - 28, 2016.

Impact/Purpose:

The science of microRNAs is rapidly advancing. These molecules are now know to be intimately involved in biological signaling, by directly effecting an endpoint, modifying the ability of mediators to effect signaling, or through negative and positive feedback loops. As such, they increasingly are being recognized as important components of adverse outcome pathways. They also can serve as sensitive biomarkers of adverse outcomes or bioindiators of exposure. The purpose of this presentation is to review these different miRNA roles and their applications to environmental health, as well as point out challenges and opportunities for their use in risk assessment.

Description:

Of the known epigenetic mechanisms, non-coding RNA and more specifically, microRNA (miRNA), offer the most immediate promise for risk assessment applications because these molecules can serve as excellent biomarkers of toxicity. The advantages of miRNA versus more classical protein toxicity biomarkers include: greater stability and earlier appearance in biofluids that can be obtained by relatively non-invasive approaches; tissue- and/or cell-specific expression patterns; evolutionary conservation in both sequence and function across species; and novel technologies for sensitive and accurate quantification. Further, information on individual miRNA is readily available through databases such as miRBase and others. Thus miRNA biomarkers offer substantial benefits in terms of cost, time, convenience, sensitivity, and specificity when assessing environmental-induced toxicity in model systems or human cohorts. Although this field is rapidly expanding, documented examples include associations of miR-155 with lymphocytic leukemia, miR-122 with liver toxicity; miR-206 with skeletal muscle disease; and miR-208a-3p with cardiac toxicity. Despite their promise, some challenges in using miRNAs as toxicity biomarkers remain, including the need for improved methods for normalizing miRNA measurements, translating findings of biofluid-based miRNA biomarker alterations in experimental models to human health and specific cell/tissue injury, and finally, the need to better define normal levels of miRNA in biofluids, sources of variation, and to identify and correct for possible methodological bias due to factors such as isolation and sample hemolysis.

Record Details: