Genomic and Epigenomic Biomarkers of Toxicology and Disease

The epigenome is defined as heritable biological information contained outside the DNA sequence (Dolinoy and Jirtle 2008). It consists of DNA methylation, histone modifications, and microRNAs. Non-coding RNAs (ncRNAs) regulate gene expression at the transcriptional or post-translational levels without changing the genomic DNA sequence (Li and Cui 2018).

The microRNAs form a class of single-stranded, non-coding small RNAs with an average of 22 nucleotides. They are involved in the post-transcriptional regulation of gene expression. They were discovered in 1993 by the Victor Ambros research group (Lee et al. 1993), in a study on the development of Caenorhabditis elegans . These researchers discovered that the microRNA lin-4 regulated negatively the expression of another gene, lin-14. In subsequent studies, microRNAs were identified in multiple species, including plants, worms, insects, fish, rodents, and mammals. The sequences of microRNAs in mammalian species are highly conserved (Friedman et al. 2009). The microRNAs are found in body fluids such as saliva, urine, and plasma. Schueller et al. (2018) have demonstrated that the dysregulation of microRNAs is associated with toxicity and liver diseases. The microRNAs are considered new molecules related to disease classification and prediction (Otsuka et al. 2017) and can be used as a biomarker in the prediction of liver cancer (Livingstone et al. 2019). Changes in microRNA expression after chemical exposure can be determined by microarrays and next-generation sequencing technologies. It is believed that microRNA profiling is a valuable diagnostic tool. The microRNAs can serve as excellent biomarkers of toxicity and disease.

Differentially expressed microRNAs are the most common genomic biomarkers used for drug safety. Candidates for translational 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 (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 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.

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