Superfund Research Program
Mechanisms and Biomarkers of Metal Olfactory Injury in Salmon
Project Leader: Evan P. Gallagher
Co-Investigators: Zhengui Xia, Daniel Storm, Rebecca B. Neumann
Grant Number: P42ES004696
Funding Period: 2009-2023
Project-Specific Links
Title: Copper-induced deregulation of microRNA expression in the zebrafish olfactory system
Accession Number: GSE46891
Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE46891
Repository: Gene Expression Omnibus (GEO)
Data Type(s): Gene Expression
Experiment Type(s): Expression profiling by array
Organism(s): Danio rerio
Summary: Although environmental trace metals, such as copper (Cu), can disrupt normal olfactory function in fish, the underlying molecular mechanisms of metal-induced olfactory injury have not been elucidated. Current research has suggested the involvement of epigenetic modifications. To address this hypothesis, we analyzed microRNA (miRNA) profiles in the olfactory tissues of Cu-exposed zebrafish. Our data revealed 2, 10, and 28 differentially expressed miRNAs in a dose response pattern to three increasing Cu concentrations. Numerous deregulated miRNAs were involved in neurogenesis (let-7, miR-7a, miR-128 and miR-138), indicating a role for Cu-mediated toxicity via interference with olfactory neurogenesis. Putative gene targets of deregulated miRNAs were identified when interrogating our previously published microarray database, including those involved in olfactory cell growth and proliferation, cell death, and cell morphology. Moreover, several miRNAs (miR-203a, miR-199*, miR-16a, miR-16c, and miR-25) were inversely correlated with the depression of key genes within olfactory signal transduction pathways, which likely contributed to the inhibition of olfactory function. Our findings provide novel insight into the epigenetic regulatory mechanisms of metal-induced neurotoxicity of fish olfactory system, and identify novel miRNA biomarkers of metal exposures.
Publication(s) associated with this dataset:- Wang L, Bammler TK, Beyer RP, Gallagher EP. 2013. Copper-induced deregulation of microRNA expression in the zebrafish olfactory system. Environ Sci Technol 47(13):7466-7474. doi:10.1021/es400615q PMID:23745839 PMCID:PMC4750873