MicroRNA-877-5p is involved in the trovafloxacin-induced liver injury.

Trovafloxacin develops severe hepatotoxicity; however, the underlying mechanism of the trovafloxacin-induced liver injury has not been cleared. It has been shown that microRNAs (miRNAs) can be involved in the development of drug-induced liver injuries. We performed a miRNA microarray analysis to identify hepatic miRNAs that were induced or reduced by trovafloxacin in mice. It was demonstrated that miR-877-5p was the most increased miRNA in the mouse liver 24h after the trovafloxacin administration. To investigate the role of miR-877-5p in the liver, we established miR-877-5p-overexpressed HepG2 cells. Microarray analysis detected altered expressions in 2077 (>2-fold) and 1547 (<0.5-fold) genes in the miR-877-5p overexpressing cells compared to the mock cells. Especially, SLCO4C1, PEPCK, MT1M, HIST1H2BM, LGI1, and PLA2G2A were markedly increased or decreased in the miR-877-5p overexpressing cells. We conducted a correlation analysis between the expression levels of miR-877-5p and the six genes in eight miR-877-5p stably-expressed clones. It was shown that the PEPCK expression levels were correlated with miR-877-5p expression levels. PEPCK is associated with development of apoptotic cell death; therefore, the increased miR- 877-5p-induced PEPCK can be a trigger that is involved in the development of trovafloxacin-induced liver injury.