title: MiRNA profiling provides insights on adverse effects of Cr(VI) in the midgut tissues of Drosophila melanogaster.
abstract: 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 5.0-20.0 μg/ml of Cr(VI) for 24 and 48 h. 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.
authors.affiliation: Embryotoxicology Section, CSIR-Indian Institute of Toxicology Research, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110 001, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Chandra
authors.affiliation: Embryotoxicology Section, CSIR-Indian Institute of Toxicology Research, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Pandey
authors.affiliation: Embryotoxicology Section, CSIR-Indian Institute of Toxicology Research, Lucknow 226001, Uttar Pradesh, India. Electronic address: dkchowdhuri@iitr.res.in.
authors.forename: Debapratim Kar
authors.initials: DK
authors.lastname: Chowdhuri
mesh_terms: D000818:Animals; D002857:Chromium / Q000633:toxicity*; D004249:DNA Damage; D004260:DNA Repair; D004331:Drosophila melanogaster / Q000187:drug effects*; D041981:Gastrointestinal Tract / Q000187:drug effects*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007814:Larva / Q000187:drug effects; D035683:MicroRNAs / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C586149:MIRN314 microRNA, Drosophila; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D002857:Chromium; C074702:chromium hexavalent ion
keywords: Cr(VI); DNA damage; Drosophila; MicroRNA; Microarray