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miRNA 谱分析揭示了 Cr(VI) 对黑腹果蝇中肠组织的不良影响。

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

机构信息

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.

Embryotoxicology Section, CSIR-Indian Institute of Toxicology Research, Lucknow 226001, Uttar Pradesh, India.

出版信息

J Hazard Mater. 2015;283:558-67. doi: 10.1016/j.jhazmat.2014.09.054. Epub 2014 Oct 5.

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.

摘要

六价铬(Cr(VI))是一种众所周知的环境化学物质,据报道会对暴露于其中的生物体造成多种不良影响,包括基因组不稳定和致癌作用。尽管有关于 Cr(VI) 诱导毒性的潜在机制的信息,但关于表观遗传机制对毒性的调节作用的研究是有限的。因此,我们假设 Cr(VI) 暴露的果蝇(一种遗传上易于处理的模式生物)中的全局 miRNA 谱分析将提供有关失调 miRNA 及其靶向基因和相关过程的信息。将黑腹果蝇(Oregon R(+))的三龄幼虫暴露于 5.0-20.0μg/ml 的 Cr(VI) 中 24 和 48 小时。在 Agilent 平台上进行 miRNA 谱分析后,发现 36 个差异表达的 miRNA 中有 28 个明显失调,靶向主要的生物学过程,如 DNA 损伤修复、氧化还原过程、发育和分化。在 DNA 修复中,mus309 和 mus312 的下调、氧化还原中的 acon 和应激激活的 MAPK 级联中的 pyd 分别属于这些基因本体类别的下调,同时 dme-miR-314-3p、dme-miR-79-3p 和 dme-miR-12-5p 的上调证实了它们对 Cr(VI) 暴露的功能参与。这些发现很重要,因为果蝇中的大多数靶基因在人类中都有功能同源物。该研究进一步推荐果蝇作为一种模型,以探索 miRNA 在异生物质诱导毒性中的作用。

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