Journal des biomarqueurs moléculaires et du diagnostic

Using microRNA as Biomarkers of Drug-Induced Liver Injury

Abstract

William F. Salminen, Xi Yang, Qiang Shi and Donna L. Mendrick

MicroRNAs (miRNA) are small non-coding RNAs that regulate gene expression post-transcriptionally. They bind to complementary sequences on target mRNA and typically down regulate expression or increase the rate of degradation; however, the roles of miRNA are still evolving and some miRNA have been shown to increase specific gene translation. miRNA holds a unique position among RNA for use as a biomarker due to its unique stability. Unlike mRNA, miRNA has been shown to be remarkably stable in a variety of tissues and body fluids. This greatly facilitates the use of miRNAs as clinical biomarkers of disease and injury since sample handling and processing is much less problematic when compared to mRNA. miRNA expression profiles have been extensively investigated for distinguishing cancerous vs. non-cancerous tissue. Taking this approach one step further, profiles of miRNA in cell-free body fluids have also been able to distinguish patients with different types of cancer and even provide prognostic information about disease outcome. The rationale behind this approach is that cancerous masses release miRNA into the systemic circulation and changes in the pattern and amount of miRNA can be used to detect the type of cancer. A recent extension of this approach is using miRNA in cell-free body fluids to detect organ injury. Several studies have shown increased serum levels of specific miRNA after myocardial or hepatocellular injury. Since some miRNA exhibit tissue specific expression, it is possible that miRNA profiles could be used to not only identify gross organ injury but also distinguish between different types of organ injury (e.g., heart vs. liver). This article will provide an overview of the role of miRNA in the cell, review the literature on using miRNA profiles to identify organ injury, and highlight the potential use of miRNA for assessing drug-induced liver injury. It should be noted that at the time of this writing, none of the profiles have been qualified for clinical use by the FDA.