title: MicroRNA-125b-5p mimic inhibits acute liver failure.
abstract: The lack of broad-spectrum anti-acute liver failure (ALF) therapeutic agents contributes to ALF-related mortality. MicroRNAs (miRNAs) are suggested to be potent serum biomarkers for ALF, but their functional and therapeutic relevance in ALF are unclear. Here we show an unbiased approach, using two complementary miRNA screens, to identify miRNAs that can attenuate ALF. We identify miR-125b-5p as a regulator of cell death that attenuates paracetamol-induced and FAS-induced toxicity in mouse and human hepatocytes. Importantly, administration of miR-125b-5p mimic in mouse liver prevents injury and improves survival in models of ALF. Functional studies show that miR-125b-5p ameliorates ALF by directly regulating kelch-like ECH-associated protein 1, in turn elevating expression of nuclear factor-E2-related factor 2, a known regulator in ALF. Collectively, our findings establish miR-125b-5p as an important regulator of paracetamol-induced and FAS-induced cell death. Thus, miR-125b-5p mimic may serve as a broad-spectrum therapeutic attenuator of cell death during ALF.
authors.affiliation: Research Group MicroRNA in Liver Regeneration, Cluster of Excellence REBIRTH, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany.|Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany.
authors.forename: Dakai
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany.|Twincore Centre for Experimental and Clinical Infection Research, Feodor-Lynen-Strasse 7, 30625 Hannover, Germany.
authors.forename: Qinggong
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany.|Twincore Centre for Experimental and Clinical Infection Research, Feodor-Lynen-Strasse 7, 30625 Hannover, Germany.
authors.forename: Asha
authors.initials: A
authors.lastname: Balakrishnan
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Bantel
authors.affiliation: Pediatric Hematology and Oncology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Jan-Henning
authors.identifier: 0000-0002-1070-0727
authors.initials: JH
authors.lastname: Klusmann
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany.|Twincore Centre for Experimental and Clinical Infection Research, Feodor-Lynen-Strasse 7, 30625 Hannover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Ott
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany.|Translational Hepatology and Stem Cell Biology, Cluster of Excellence REBIRTH, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Cantz
authors.affiliation: Research Group MicroRNA in Liver Regeneration, Cluster of Excellence REBIRTH, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany.|Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany.
authors.forename: Amar Deep
authors.initials: AD
authors.lastname: Sharma
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D000072019:Kelch-Like ECH-Associated Protein 1 / Q000378:metabolism; D017114:Liver Failure, Acute / Q000378:metabolism* / Q000517:prevention & control; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000008:administration & dosage / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D061251:Primary Cell Culture; D012323:RNA Processing, Post-Transcriptional
chemical_list: D000072019:Kelch-Like ECH-Associated Protein 1; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; C527468:Mirn125 microRNA, mouse; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human