<i>miR-122</i> plays an important role in ochratoxin A-induced hepatocyte apoptosis <i>in vitro</i> and <i>in vivo</i>

Abstract

OTA can induce hepatotoxicity. Our previous research has shown that miRNAs play important roles in the OTA-induced hepatotoxicity. And <i>miR-122</i> is the most abundant miRNA in the liver and is involved in diverse biological processes. This study was performed to clarify the role of <i>miR-122</i> in OTA-induced hepatotoxicity. The expression levels of <i>miR-122</i> and the target genes were quantified by real-time PCR. The OTA-induced apoptosis of hepatocyte and HepG2 cells was evaluated using a TUNEL kit, a CCK-8 kit, a flow cytometer and Hoechst 33342. <i>miR-122</i> was inhibited in HepG2 cells. The results revealed that OTA affected rat hepatocyte apoptosis. <i>miR-122</i> decreased at 4 weeks but increased at 13 weeks in the OTA-treated livers, and increased in the OTA-treated HepG2 cells; and the mRNA levels of <i>CCNG1</i> and <i>Bcl-w</i> increased at 4 weeks and decreased at 13 weeks in the high-dose OTA-treatment groups and decreased in HepG2 cells. The apoptosis of HepG2 cells displayed a dose-related increase with OTA. However, the inhibition of <i>miR-122</i> greatly reduced OTA-induced apoptosis. <i>p53</i> decreased <i>in vivo</i> and <i>in vitro</i>. <i>miR-122</i> is a primary effector of OTA-induced hepatocyte apoptosis through the <i>CCNG1</i>/<i>p53</i> pathway and <i>Bcl-w</i>/<i>caspase-3</i> pathway <i>in vivo</i> and <i>in vitro</i>. And <i>miR-122</i> plays an important role in OTA-induced hepatotoxicity.