Recent progress in the use of microRNAs as biomarkers for drug-induced toxicities in contrast to traditional biomarkers: A comparative review.

microRNAs (miRNAs) are small non-coding RNAs with 18-25 nucleotides. They play key regulatory roles in versatile biological process including development and apoptosis, and in disease pathogenesis, for example carcinogenesis, by negatively regulating gene expression. miRNAs often exhibit characteristics suitable for biomarkers such as tissue-specific expression patterns, high stability in serum/plasma, and change in abundance in circulation immediately after toxic injury. Since the discovery of circulating miRNAs in extracellular biological fluids in 2008, there have been many reports on the use of miRNAs as biomarkers for various diseases including cancer and organ injury in humans and experimental animals. In this review article, we have summarized the utility and limitation of circulating miRNAs as safety/toxicology biomarkers for specific tissue injuries including liver, skeletal muscle, heart, retina, and pancreas, by comparing them with conventional protein biomarkers. We have also covered the discovery of miRNAs in serum/plasma and their stability, the knowledge of which is essential for understanding the kinetics of miRNA biomarkers. Since numerous studies have reported the use of these circulating miRNAs as safety biomarkers with high sensitivity and specificity, we believe that circulating miRNAs can promote pre-clinical drug development and improve the monitoring of tissue injuries in clinical pharmacotherapy.