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 48 h after exposure to MC-LR. We observed a rapid increase of miR-122-5p levels 8 h 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.

Microcystin-LR-Triggered Neuronal Toxicity in Whitefish Does Not Involve MiR124-3p

“…Drug-induced liver injury can be monitored through traditional blood enzymes (ALT, AST) or more sensitively through miRNA quantification. Our previous study on whitefish exposed to MC-LR showed increased liver-specific miRNA plasma levels in fish, which is similar to the outcome acetaminophen induced in mammals (Florczyk et al 2016 ). MiR122-5p levels were elevated as early as 8 h after exposure.…”

Changes in Physiological Parameters, Lipid Metabolism, and Expression of MicroRNAs in Genetically Improved Farmed Tilapia (Oreochromis niloticus) With Fatty Liver Induced by a High-Fat Diet

“…Many studies have revealed that miRNAs are important regulators of liver function in teleost fish ( Her et al, 2011 ; Mennigen et al, 2014 ; Zhang et al, 2014 ; Wang et al, 2016 ). Particularly, miR-122 has been shown as a biomarker of liver injury ( Florczyk et al, 2016 ) and play a role in hepatic lipid metabolism in grass carp ( Wang et al, 2016 ), rainbow trout ( Oncorhynchus mykiss ) ( Mennigen et al, 2014 ), and zebrafish ( Danio rerio ) ( Her et al, 2011 ). Analyses of our deep sequencing data revealed that some miRNAs were differentially expressed in the liver between GIFT fed a HFD and those fed a normal-fat diet (NFD) for 60 days.…”

Illumina Sequencing Reveals Aberrant Expression of MicroRNAs and Their Variants in Whitefish (Coregonus lavaretus) Liver after Exposure to Microcystin-LR

“…The versatile role of miRNAs has sparked the interest of our group in utilizing miRNAs as potential diagnostic [ 35 , 36 ] and prognostic [ 37 , 38 ] biomarkers of MC-LR toxicity and liver injury in fish. In our initial study, we showed that 5 out of 8 miRNAs, MiRlet7c, MiR16a, MiR21a, MiR34a and MiR122, were deregulated in the liver of whitefish ( Coregonus lavaretus ) after short-term (2 d) exposure to MC-LR [ 35 ].…”