Alteration of the microRNA-122 regulatory network in rat models of hepatotoxicity

• miRNA-122 levels decrease during experimental hepatotoxicity.
• Altered miRNA-122 levels are not associated with changes in miRNA processing pathway.
• miRNA-122 expression levels are under transcriptional control in hepatotoxicity.
• Decreased miRNA-122 levels are associated with liver recovery after damage.

MicroRNAs are small RNA molecules that post-transcriptionally regulate gene expression. MicroRNA-122 is the most abundant and specific liver microRNA. Hepatotoxicity involves a significant alteration of liver gene expression. The aim of this work was to evaluate the microRNA-122 regulatory network in models of hepatotoxicity induced by thioacetamide or carbon tetrachloride. We report that the toxins decreased the expression of microRNA-122, which corresponded with an increase in two target genes: Cyclin G1 and the cationic amino acid transporter CAT-1. We found a decreased expression of its precursor, pri-microRNA-122, and of the transcription factors that specifically bind its promoter: CCAAT/enhancer-binding protein alpha, and members of the hepatocyte nuclear factor family. Therefore, microRNA-122 expression levels are under transcriptional control during hepatotoxicity. We propose that the changes observed are associated with the liver response to cope with the injury caused by the hepatotoxins, likely through a cell proliferation process to repair the damaged tissue.

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