Ethanol exposure induces upregulation of specific microRNAs in zebrafish embryos.
Prenatal exposure to ethanol leads to a myriad of developmental disorders known as fetal alcohol spectrum disorder, often characterized by growth and mental retardation, central nervous system damage, and specific craniofacial dysmorphic features. The mechanisms of ethanol toxicity are not fully understood, but exposure during development affects the expression of several genes involved in cell cycle control, apoptosis, and transcriptional regulation. MicroRNAs (miRNAs) are implicated in some of these processes, however, it is not yet clear if they are involved in ethanol-induced toxicity. In order to clarify this question, we have exposed zebrafish embryos to ethanol and evaluated whether a miRNA deregulation signature could be obtained. Zebrafish embryos were exposed to 1 and 1.5% of ethanol from 4 h postfertilization (hpf) to 24 hpf. The miRNA expression profiles obtained reveal significant miRNA deregulation and show that both ethanol concentrations upregulate miR-153a, miR-725, miR-30d, let-7k, miR-100, miR-738, and miR-732. Putative gene targets of deregulated miRNAs are involved in cell cycle control, apoptosis, and transcription, which are the main processes affected by ethanol toxicity. The conservation of affected mechanisms among vertebrates leads us to postulate that similar miRNA deregulation occurs in humans, highlighting a relevant role of miRNAs in ethanol toxicology.
RNA Biology Laboratory, Department of Biology, CESAM, University of Aveiro, 3810-193 Aveiro, Portugal.
Ana Raquel
AR
Soares
Patrícia M
PM
Pereira
Violeta
V
Ferreira
Marisa
M
Reverendo
João
J
Simões
Ana Rita
AR
Bezerra
Gabriela R
GR
Moura
Manuel A S
MA
Santos
D000014:Abnormalities, Drug-Induced / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002492:Central Nervous System Depressants / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D035683:MicroRNAs / Q000187:drug effects* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects*; D015027:Zebrafish
D015415:Biomarkers; D002492:Central Nervous System Depressants; D035683:MicroRNAs; D000431:Ethanol