MiR-122-5p as a plasma biomarker of liver injury in fish exposed to microcystin-LR.

Abstract

Recent studies have shown the presence of large amounts of microRNAs (miRNAs; miRs) from damaged cells in the peripheral blood. In this study, we investigated the levels of miRNAs circulating in the blood plasma of whitefish (Coregonus lavaretus) after exposure to microcystin-LR. We used real-time PCR to examine the relative expression of plasma levels of 4 miRNAs (miR-122-5p and let-7c-5p, the liver-enriched microRNAs, miR-148a-3p which promotes the hapatospecific phenotype in mammals, and miR-92a-3p, a cell proliferation and angiogenesis promoter, potentially hepatocarcinogenic) during the first 48h after exposure to MC-LR. We observed a rapid increase of miR-122-5p levels 8h after exposure (P<0.05), which continued to the end of the experiment. Our results demonstrated that the plasma miR-122-5p was indicative of MC-LR-induced liver injury, exhibiting areas under the curve close to 1 in ROC analysis (AUC=0.976, P<0.001). Although plasma levels of miR-148a-3p and miR-92a-3p were significantly elevated by the end of the experiment, their discriminative power was lower than reported for the miR-122-5p. Based on these results and reports on miRNA-based diagnosis of liver injuries in mammals, plasma miR-122-5p could be considered as a robust, new generation diagnostic biomarker in fish, helpful for the non-invasive diagnosis of liver damage.