Functional investigation of MiR92b-3p for diagnosis and miRNA-based cure in chemically induced liver injury in fish: a project description

The continued lack of knowledge concerning the molecular background of adverse effects caused by microcystin-LR (MC-LR) is surprising. This toxin requires additional attention, not only for its ability to cause acute poisoning, but also for its ability to initiate cancer in acute doses, and potentially, to promote cancer via chronic exposure to low concentrations in drinking water. Our recent studies on whitefish (Coregonus lavaretus) revealed that long-term exposure to MC-LR resulted in severe liver injury, followed by regeneration of the liver and its unexpected resilience to further toxin uptake. These effects were accompanied by perturbations of hepatic microRNAs (miRNAs) that have target genes involved in cytoskeletal remodeling, cell metabolism, cell cycle regulation, and apoptosis. Among the most pronounced individual alterations, the reduction of MiR92b-3p expression was the most remarkable, and we suggest roles for the miRNA in the aberrant processes of liver cells. This project addresses potential involvement of MiR92b-3p in the as yet unknown regulatory network of MC-induced hepatotoxicity in fish. After a suite of biochemical, physiological, anatomical, and transcriptomic analyses in vitro and in vivo, we will show how MiR92b-3p works in a damaged liver and which processes it targets. Finally, the research will confirm if and how MiR92b-3p can be targeted therapeutically. We expect it to be shown effective enough to pave a way for its use as a tool for treatment of liver damage in fish. What is more, the RNA-based silencing technique that will be used should yield exciting data for our understanding of the system-level biology of vertebrates