microRNA biomarkers for liver injury have been proposed (Li et al. 2021). Urinary microRNA biomarkers of drug-induced kidney injury have been suggested (Chorley et al. 2021). Recent studies have provided evidence that tumor-related genes regulated through DNA methylation and microRNA are involved in the occurrence of hepatocellular carcinoma (Lin et al. 2019).
Circular RNAs
Circular RNAs (circRNAs) are a class of closed, long, non-coding RNAs with stable expression in various tissues in different mammalian species. These most recently discovered ncRNAs are present abundantly in the transcriptome of eukaryotic cells. They play an important role in the regulation of gene expression (Shao and Jiang 2021) and in tumor development (Jeyaraman et al. 2019). Therefore they are considered potential biomarkers of toxicity and disease (Jeyaraman et al. 2019; Shao and Jiang 2021).
The Need for a Book on Genomic and Epigenomic Biomarkers for Predictive Toxicity and Disease
The rate of publications during the last few years has demonstrated that the developments of genomic and epigenomic biomarkers for predictive toxicity and disease are moving very rapidly, and therefore there is a need for new means to report the updated current status of this new area of research. As editor of Genomic and Epigenomic Biomarkers for Toxicology and Disease: Clinical and Therapeutic Actions, it gives me great pride, pleasure, and honor to introduce this unique book, which encompasses many aspects of genomic and epigenomic biomarker research never brought together in one publication before.
References
1 Califf, R.M. (2018). Biomarker definitions and their applications. Exp. Biol. Med. (Maywood) 243 (3): 213–221. Published online 2018 Feb 6. https://doi.org/10.1177/1535370217750088.
2 Chorley, B.N., Ellinger-Ziegelbauer, H., Tackett, M., Simutis, F.J., Harrill, A.H., McDuffie, J., Atabakhsh, E., Nassirpour, R., Whiteley, L.O., Léonard, J., Carswell, G.K., Harpur, E., Chen, C.L., and Gautier, J. (2021). Urinary miRNA biomarkers of drug-induced kidney injury and their site specificity within the nephron. Toxicol. Sci. 180 (1): 1–16. https://doi.org/10.1093/toxsci/kfaa181.
3 de Gannes, M., Ko, C., Zhang, X., Biesiada, J., Niu, L., Koch, S.E., Medvedovic, M., Rubinstein, J., and Puga, A. (2020). Dioxin disrupts dynamic DNA methylation patterns in genes that govern cardiomyocyte maturation. Toxicol. Sci. 178 (2): 325–337. https://doi.org/10.1093/toxsci/kfaa153.
4 Dolinoy, D.C. and Jirtle, R.L. (2008). Environmantal epigenomics in human health and disease. Environ. Mol. Mutagen. 49 (1): 4–8.
5 Friedman, R.C., Farh, K.K., Burge, C.B., and Bartel, D.P. (2009). Most mammalian mRNAs are conserved targets of microRNAs. Genom. Res. 19: 92–105.
6 Jeyaraman, S., Hanif, E.A.M., Ab Mutalib, N.S., Jamal, R., and Abu, N. (2019). Circular RNAs: Potential regulators of treatment resistance in human cancers. Front. Genet. 10: 1369.
7 Jones, P.A. (2012). Functions of DNA methylation: Islands, start sites, gene bodies and beyond. Nat. Rev. Genet. 13: 484–492.
8 Judson, R., Houck, K., Martin, M., Richard, A.M., Knudsen, T.B., Shah, I., Little, S., Wambaugh, J., Setzer, R.W., Kothya, P., Phuong, J., File, D., Smith, D., Reif, D., Rotroff, D., Kleinstreuer, N., Sipes, N., Xia, M., Huang∣, R., Crofton, K., and Thomas, R.S. (2016). Analysis of the effects of cell stress and cytotoxicity on in vitro assay activity across a diverse chemical and assay space. Toxicol. Sci. 152 (2): 323–339.
9 Judson, R., Kavlock, R., Martin, M., Reif, D., Houck, K., Knudsen, T., Richard, A., Tice, R.R., Whelan, M., Xia, M., Huang, R., Austin, C., Daston, G., Hartung, T., Fowle, J.R., Wooge, W., Tong, W., and Dix, D. (2013). Perspectives on validation of high-throughput assays supporting 21st century toxicity testing. ALTEX 30 (1): 51–56.
10 Krewski, D., Acosta, D., Andersen, M., Anderson, H., Bailar, J.C., Boekelheide, K., Brent, R., Charnley, G., Cheung, V.G., Green, S., Kelsey, K.T., Kerkvliet, N.I., Li, A.A., McCray, L., Meyer, O., Patterson, R.D., Pennie, W., Scala, R.A., Solomon, G.M., Stephens, M., Yager, J., and Zeise, L. (2010). Toxicity testing in the 21st century: A vision and a strategy. J. Toxicol. Environ. Health. B. Crit. Rev. 2010 Feb 13 (0): 51–138. 10.1080/10937404.2010.483176.
11 Lee, R.C., Feinbaum, R.L., and Ambros, V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75: 843–854.
12 Li, C.Y. and Cui, J.Y. (2018). Regulation of protein-coding gene and long noncoding RNA pairs in liver of conventional and germ-free mice following oral PBDE exposure. Plos One 13: e0201387.
13 Li, D., Knox, B., Gong, B., Chen, S., Guo, L., Liu, Z., Tong, W., and Ning, B. (2021). Identification of translational microRNA biomarker candidates for ketoconazole-induced liver injury using next-generation sequencing. Toxicol. Sci. 179 (1): 31–43. https://doi.org/10.1093/toxsci/kfaa162.
14 Lin, C., Yuan, G., Hu, Z., Zeng, Y., Qiu, X., Yu, H., and He, S. (2019). Bioinformatics analysis of the interactions among lncRNA, miRNA and mRNA expression, genetic mutations and epigenetic modifications in hepatocellular carcinoma. Mol. Med. Rep. 19: 1356–1364. https://doi.org/10.3892/mmr.2018.9728.
15 Livingstone, M.C., Johnson, N.M., Roebuck, B.D., Kensler, T.W., and Groopman, J.D. (2019). Serum miR-182 is a predictive biomarker for dichotomization of risk of hepatocellular carcinoma in rats. Mol. Carcinog. 58: 2017–2025. https://doi.org/10.1002/mc.23093.
16 NAS (U.S. National Academy of Sciences). (2007). Toxicity Testing in the 21st Century: A Vision and A Strategy. Washington, DC: National Academy Press.
17 Otsuka, M., Kishikawa, T., Yoshikawa, T., Yamagami, M., Ohno, M., Takata, A., Shibata, C., Ishibashi, R., and Koike, K. (2017). MicroRNAs and liver disease. J. Hum. Genet. 62: 75–80. https://doi.org/10.1038/jhg.2016.53.
18 Robb, M.A., McInnes, P.M., and Califf, R.M. (2016). Biomarkers and surrogate endpoints: Developing common terminology and definitions. JAMA 2016 315: 1107–1108.
19 Schueller, F., Roy, S., Vucur, M., Trautwein, C., Lurdde, T., and Roderberg, C. (2018). The role of miRNA in the pathophyisiology of liver diseases and toxicity. Int. J. Mol. Sci. 19: 261–269.
20 Shao, Y. and Jiang, Y. (2021). Circular RNAs in Toxicology. Toxicol. Sci. 179 (2): 149–161. https://doi.org/10.1093/toxsci/kfaa173.
21 Woodcock, J. (2009). Chutes and ladders on the critical path: Comparative effectiveness, product value, and the use of biomarkers in drug development. Clin. Pharmacol. Ther. 86 (1): 12–14.
2 MicroRNAs as Non-invasive Biomarkers of Toxicity and Chemical Hazard Genomic and Epigenomic Biomarkers of Toxicology and Disease
Gail M. Nelson and Brian N. Chorley
Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27709
Introduction
MicroRNAs (miRNAs) are short, non-coding RNAs whose primary known function is to regulate the transcription and translation of messenger RNA. Targeting occurs through sequence specificity; however, this interaction is not limited to a single gene. Rather, a particular miRNA can regulate hundreds of genes. In addition, a transcript may be targeted by multiple miRNAs. As a result, it is estimated that between 30% and 80% of all transcribed genes in mammals may be