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环境化学物质在人类基因组中对 miRNA 靶标的优先调控。

Preferential regulation of miRNA targets by environmental chemicals in the human genome.

机构信息

Key laboratory of Photosynthesis and Environmental Molecular Physiology, the Institute of Botany, Chinese Academy of Sciences, Beijing, 100093, China.

出版信息

BMC Genomics. 2011 May 18;12:244. doi: 10.1186/1471-2164-12-244.

DOI:10.1186/1471-2164-12-244
PMID:21592377
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3118786/
Abstract

BACKGROUND

microRNAs (miRNAs) represent a class of small (typically 22 nucleotides in length) non-coding RNAs that can degrade their target mRNAs or block their translation. Recent disease research showed the exposure to some environmental chemicals (ECs) can regulate the expression patterns of miRNAs, which raises the intriguing question of how miRNAs and their targets cope with the exposure to ECs throughout the genome.

RESULTS

In this study, we comprehensively analyzed the properties of genes regulated by ECs (EC-genes) and found miRNA targets were significantly enriched among the EC-genes. Compared with the non-miRNA-targets, miRNA targets were roughly twice as likely to be EC-genes. By investigating the collection methods and other properties of the EC-genes, we demonstrated that the enrichment of miRNA targets was not attributed to either the potential collection bias of EC-genes, the presence of paralogs, longer 3'UTRs or more conserved 3'UTRs. Finally, we identified 1,842 significant concurrent interactions between 407 miRNAs and 497 ECs. This association network of miRNAs-ECs was highly modular and could be separated into 14 interconnected modules. In each module, miRNAs and ECs were closely connected, providing a good method to design accurate miRNA markers for ECs in toxicology research.

CONCLUSIONS

Our analyses indicated that miRNAs and their targets played important roles in cellular responses to ECs. Association analyses of miRNAs and ECs will help to broaden the understanding of the pathogenesis of such chemical components.

摘要

背景

microRNAs(miRNAs)是一类小的(通常长度为 22 个核苷酸)非编码 RNA,可以降解其靶 mRNA 或阻止其翻译。最近的疾病研究表明,某些环境化学物质(ECs)的暴露可以调节 miRNAs 的表达模式,这引发了一个有趣的问题,即 miRNAs 和它们的靶基因如何应对 ECs 在整个基因组中的暴露。

结果

在这项研究中,我们全面分析了受 ECs 调控的基因(EC-基因)的特性,发现 miRNA 靶基因在 EC-基因中显著富集。与非 miRNA 靶基因相比,miRNA 靶基因成为 EC-基因的可能性大约是两倍。通过研究 EC-基因的收集方法和其他特性,我们证明了 miRNA 靶基因的富集不是由于 EC-基因的潜在收集偏差、旁系同源物的存在、更长的 3'UTR 或更保守的 3'UTR 所致。最后,我们确定了 407 个 miRNA 和 497 个 EC 之间 1842 个显著的并发相互作用。miRNAs-ECs 的这种关联网络高度模块化,可以分为 14 个相互连接的模块。在每个模块中,miRNAs 和 ECs 紧密相连,为毒理学研究中 ECs 的准确 miRNA 标志物设计提供了一种很好的方法。

结论

我们的分析表明,miRNAs 和它们的靶基因在细胞对 ECs 的反应中发挥了重要作用。miRNAs 和 ECs 的关联分析将有助于拓宽对这些化学物质成分发病机制的理解。

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