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

• Autorzy: Brzuzan P. , Woźny M. , Florczyk M.

Identyfikatory

DOI

10.14799/ebms287

• Języki publikacji: EN

Abstrakty

EN

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.

Słowa kluczowe

EN

hepatotoxicity mechanism; liver regeneration; Locked Nucleic Acids; microcystin; RNA interference; toxicogenomics; whitefish

• Wydawca: University of Warmia and Mazury in Olsztyn, Poland
• Czasopismo: Environmental Biotechnology
• Rocznik: 2016
• Tom: Vol. 12, No. 2
• Strony: 40--42
• Opis fizyczny: Bibliogr. 2 poz.

Twórcy

autor

Brzuzan P.

• Department of Environmental Biotechnology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, Słoneczna 45G, 10-709 Olsztyn, Poland; Phone [phone]; Fax: [phone]

autor

Woźny M.

• Department of Environmental Biotechnology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, Poland

autor

Florczyk M.

• Department of Environmental Biotechnology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, Poland

Bibliografia

• Brzuzan, P., M. Florczyk, A. Łakomiak, M. Woźny. 2016. Illumina sequencing reveals aberrant expression of microRNAs and their variants in whitefish (Coregonus lavaretus) liver after exposure to microcystin-LR. PLOS ONE 11: e0158899.
• Woźny, M., B. Lewczuk, N. Ziółkowska, P. Gomułka, S. Dobosz, A. Łakomiak, M. Florczyk, P. Brzuzan. 2016. Intraperitoneal exposure of whitefish to microcystin-LR induces rapid liver injury followed by regeneration and resilience to subsequent exposures. Toxicology and Applied Pharmacology 313: 68-87.