Diagnostic potential of serum miR-532-3p as a circulating biomarker for experimental intrinsic drug-induced liver injury by acetaminophen and cisplatin in rats

Evaluating tissue injury largely depends on serum biochemical analysis despite insufficient tissue specificity and low sensitivity. Therefore, attention has been paid to the potential of microRNAs (miRNAs) to overcome the limitations of the current diagnostic tools, as tissue-enriched miRNAs are detected in the blood upon tissue injury. First, using a cisplatin-injected rats, we screened a specific pattern of altered hepatic miRNAs and their target mRNAs. Subsequently, we identified novel liver-specific circulating miRNAs for drug-induced liver injury by comparing miRNA expression changes in organs and serum. RNA sequencing revealed that 32 hepatic miRNAs were differentially expressed (DE) in the cisplatin-treated group. Furthermore, among the 1217 targets predicted using miRDB on these DE-miRNAs, 153 hepatic genes involved in different liver function-related pathways and processes were found to be dysregulated by cisplatin. Next, comparative analyses of the liver, kidneys, and serum DE-miRNAs were conducted to select circulating miRNA biomarker candidates reflecting drug-induced liver injury. Finally, among the four liver-specific circulating miRNAs selected based on their expression patterns in tissue and serum, miR-532-3p was increased in the serum after cisplatin or acetaminophen administration. Our findings suggest that miR-532-3p is potential as a serum biomarker for identifying drug-induced liver injury, leading to the accurate diagnosis.

Automated summary

Evaluation of tissue injury currently relies on serum biochemical analysis, which lacks tissue specificity and sensitivity. MicroRNAs (miRNAs) have been proposed as potential diagnostic tools to overcome these limitations, as tissue-enriched miRNAs can be detected in the blood after tissue injury. In this study, we screened specific patterns of altered hepatic miRNAs and their target mRNAs in cisplatin-injected rats, and identified novel liver-specific circulating miRNAs for drug-induced liver injury. Comparative analyses of miRNA expression changes in organs and serum were conducted, and miR-532-3p was identified as a potential serum biomarker for drug-induced liver injury.