miRNA profiling provides insights on adverse effects of Cr(VI) in the midgut tissues of Drosophila melanogaster

•miRNAs were significantly mis-regulated in Cr(VI) fed Drosophila melanogaster.•Majorly altered miRNAs targeted oxidative stress, DNA damage and repair processes.•Mis-regulation of miRNAs was in agreement with their putative target genes.•miRNAs profiling connoted the association of miRNAs in Cr(VI)...

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Veröffentlicht in:Journal of hazardous materials 2015-01, Vol.283, p.558-567
Hauptverfasser: Chandra, Swati, Pandey, Ashutosh, Chowdhuri, Debapratim Kar
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Sprache:eng
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Zusammenfassung:•miRNAs were significantly mis-regulated in Cr(VI) fed Drosophila melanogaster.•Majorly altered miRNAs targeted oxidative stress, DNA damage and repair processes.•Mis-regulation of miRNAs was in agreement with their putative target genes.•miRNAs profiling connoted the association of miRNAs in Cr(VI) induced toxicity.•Study further tempts to explore the role of miRNAs in Cr(VI) induced toxicity. Cr(VI), a well-known environmental chemical, is reported to cause various adverse effects on exposed organisms including genomic instability and carcinogenesis. Despite available information on the underlying mechanism of Cr(VI) induced toxicity, studies regarding toxicity modulation by epigenetic mechanisms are limited. It was therefore, hypothesized that the global miRNA profiling in Cr(VI) exposed Drosophila, a genetically tractable model organism, will provide information about mis-regulated miRNAs along with their targeted genes and relevant processes. Third instar larvae of Drosophila melanogaster (Oregon R+) were exposed to 5.0–20.0μg/ml of Cr(VI) for 24 and 48h. Following miRNA profile analysis on an Agilent platform, 28 of the 36 differentially expressed miRNAs were found to be significantly mis-regulated targeting major biological processes viz., DNA damage repair, oxidation–reduction processes, development and differentiation. Down-regulation of mus309 and mus312 under DNA repair, acon to oxidation–reduction and pyd to stress activated MAPK cascade respectively belonging to these gene ontology classes concurrent with up-regulation of dme-miR-314-3p, dme-miR-79-3p and dme-miR-12-5p confirm their functional involvement against Cr(VI) exposure. These findings assume significance since majority of the target genes in Drosophila have functional homologues in humans. The study further recommends Drosophila as a model to explore the role of miRNAs in xenobiotic induced toxicity.
ISSN:0304-3894
1873-3336
DOI:10.1016/j.jhazmat.2014.09.054