Copper-Induced Deregulation of microRNA Expression in the Zebrafish Olfactory System

Abstract

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 system of Cu-exposed zebrafish. Our data revealed 2, 10, and 28 differentially expressed miRNAs in a dose-response manner corresponding to three increasing Cu concentrations. Numerous deregulated miRNAs were involved in neurogenesis (e.g. let-7, miR-7a, miR-128 and miR-138), indicating a role for Cu-mediated toxicity via interference with neurogenesis processes. Putative gene targets of deregulated miRNAs were identified when interrogating our previously published microarray database, including those involved in cell growth and proliferation, cell death, and cell morphology. Moreover, several miRNAs (e.g. miR-203a, miR-199*, miR-16a, miR-16c, and miR-25) may contribute to decreased mRNA levels of their host genes involved in olfactory signal transduction pathways and other critical neurological processes via a post-transcriptional mechanism. Our findings provide novel insight into the epigenetic regulatory mechanisms of metal-induced neurotoxicity of the fish olfactory system, and identify novel miRNA biomarkers of metal exposures.

Current evidence for a role of epigenetic mechanisms in response to ionizing radiation in an ecotoxicological context

“…The first definition of epigenetics, as 'the causal interactions between genes and their products, which brings the phenotype into being', was provided by Waddington (1939) long before any mechanistic understanding of the relevant processes had developed. This definition has since been refined.…”

“…Consequently it has been proposed that rapid adaptation may be more strongly linked to epigenetic processes in the development of locally adapted phenotypes at polluted sites (Kovalchuk et al 2003). (Kure et al 2013;Wang et al 2013;Song et al 2012) and histone modifications (Raut and Sainis 2012;Mondal et al 2016). Changes in microRNA expression have further been shown to be involved in metabolism following starvation and the transfer of longevity (Greer et al 2011;Katz et al 2009;Rechavi et al 2014).…”

MiR-205 Mediated Cu-Induced Lipid Accumulation in Yellow Catfish Pelteobagrus fulvidraco

“…The present study also indicated that 16 miRNAs were differentially expressed between the control and Cu-treated group. Similarly, Wang et al [ 23 ] also found that waterborne Cu exposure influenced miRNAs expression in other fish. Moreover, GO and KEGG analysis indicated that these differentially expressed miRNAs were involved in ether lipid metabolism pathway, glycerophospholipid metabolism pathway and linoleic acid metabolism pathway, which seemed to be important pathways under Cu exposure.…”

Turing Revisited: Decoding the microRNA Messages in Brain Extracellular Vesicles for Early Detection of Neurodevelopmental Disorders

“…In a zebrafish model, copper induced deregulation of miRNAs (from olfactory system tissues) involved in neurogenesis (e.g., let-7, miR-7a, miR-128, and miR-138), which suggests a role for miRNAs in copper-mediated toxicity via interference with neurogenesis processes [76]. …”