title: MiR-125b protects against ethanol-induced apoptosis in neural crest cells and mouse embryos by targeting Bak 1 and PUMA.
abstract: MicroRNAs are a class of small noncoding RNAs that have been implicated in regulation of a broad range of cellular and physiologic processes, including apoptosis. The objective of this study is to elucidate the roles of miR-125b in modulating ethanol-induced apoptosis in neural crest cells (NCCs) and mouse embryos. We found that treatment with ethanol resulted in a significant decrease in miR-125b expression in NCCs and in mouse embryos. We also validated that Bcl-2 antagonist killer 1 (Bak1) and p53-upregulated modulator of apoptosis (PUMA) are the direct targets of miR-125b in NCCs. In addition, over-expression of miR-125b significantly reduced ethanol-induced increase in Bak1 and PUMA protein expression, caspase-3 activation, and apoptosis in NCCs, indicating that miR-125b can modulate ethanol-induced apoptosis by the regulation of Bcl-2 and p53 pathways. Furthermore, microinjection of miR-125b mimic resulted in a significant increase in miR-125b expression and a decrease in the protein expression of Bak1 and PUMA in ethanol-exposed mouse embryos. Up-regulation of miR-125b also significantly reduced ethanol-induced caspase-3 activation and diminished ethanol-induced growth retardation in mouse embryos. This is the first demonstration that miR-125b can prevent ethanol-induced apoptosis and that microinjection of miRNA mimic can prevent ethanol-induced embryotoxicity.
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville Health Science Center, Louisville, KY 40292, USA; University of Louisville Alcohol Research Center, Louisville, KY 40292, USA.
authors.forename: Xiaopan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville Health Science Center, Louisville, KY 40292, USA; University of Louisville Alcohol Research Center, Louisville, KY 40292, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: University of Louisville Alcohol Research Center, Louisville, KY 40292, USA; Department of Medicine, University of Louisville, KY 40292, USA.
authors.forename: Wen-ke
authors.initials: WK
authors.lastname: Feng
authors.affiliation: Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville Health Science Center, Louisville, KY 40292, USA; University of Louisville Alcohol Research Center, Louisville, KY 40292, USA. Electronic address: shaoyu.chen@louisville.edu.
authors.forename: Shao-yu
authors.initials: SY
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009432:Neural Crest / Q000187:drug effects*; D009924:Organ Culture Techniques; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C494773:Bak1 protein, mouse; D002492:Central Nervous System Depressants; D035683:MicroRNAs; C527468:Mirn125 microRNA, mouse; C488588:PUMA protein, mouse; D025521:Tumor Suppressor Proteins; D050998:bcl-2 Homologous Antagonist-Killer Protein; D000431:Ethanol; D053148:Caspase 3
keywords: Apoptosis; Bak1; Fetal alcohol spectrum disorders; MiR-125b; Neural crest cells; P53