Department of Occupational and Environmental Health, Central South University, Changsha, 410078, China.
Department of Radiation Biology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, AMMS, Beijing, 100850, PR China.
Environ Pollut. 2019 Apr;247:64-71. doi: 10.1016/j.envpol.2019.01.014. Epub 2019 Jan 9.
Numerous recent studies have underlined the crucial players of noncoding RNAs (ncRNAs), i.e., microRNAs(miRNAs), long noncoding RNAs(lncRNAs) and circle RNAs(circRNAs) participating in genotoxic responses induced by a wide variety of environmental genotoxicants consistently. Genotoxic-derived ncRNAs provide us a new epigenetic molecular-ecological network (MEN) insights into the underlying mechanisms regarding genotoxicant exposure and genotoxic effects, which can modify ncRNAs to render them "genotoxic" and inheritable, thus potentially leading to disease risk via epigenetic changes. In fact, the spatial structures of ncRNAs, particularly of secondary and three-dimensional structures, diverse environmental genotoxicants as well as RNA splicing and editing forma dynamic pool of ncRNAs, which constructs a MEN in cells together with their enormous targets and interactions, making biological functions more complicated. We nonetheless suggest that ncRNAs have both beneficial(positive) and harmful(negative) effects, i.e., are "double-edged" in regulating genotoxicant toxic responses. Understanding the "double-edged" effects of ncRNAs is of crucial importance for our further comprehension of the pathogenesis of human diseases induced by environmental toxicants and for the construction of novel prevention and therapy targets. Furthermore, the MEN formed by ncRNAs and their interactions each other as well as downstream targets in the cells is important for considering the active relationships between external agents (environmental toxicants) and inherent genomic ncRNAs, in terms of suppression or promotion (down- or upregulation), and engineered ncRNA therapies can suppress or promote the expression of inherent genomic ncRNAs that are targets of environmental toxicants. Moreover, the MEN would be expected to be would be applied to the mechanistic explanation and risk assessment at whole scene level in environmental genotoxicant exposure. As molecular biology evolves rapidly, the proposed MEN perspective will provide a clearer or more comprehensive holistic view.
大量最近的研究强调了非编码 RNA（ncRNA）的关键作用，即 microRNAs（miRNAs）、长非编码 RNA（lncRNAs）和环状 RNA（circRNAs），它们一致参与由各种环境遗传毒物引起的遗传毒性反应。遗传毒性衍生的 ncRNA 为我们提供了一个新的表观遗传分子生态网络（MEN），深入了解遗传毒物暴露和遗传毒性效应的潜在机制，这些机制可以修饰 ncRNA 使其具有“遗传毒性”和可遗传性，从而通过表观遗传变化潜在地导致疾病风险。事实上，ncRNA 的空间结构，特别是二级和三维结构，各种环境遗传毒物以及 RNA 剪接和编辑形式的动态 ncRNA 池，与它们的巨大靶标和相互作用一起构建了细胞中的 MEN，使生物功能更加复杂。然而，我们认为 ncRNA 既有有益（阳性）的影响，也有有害（阴性）的影响，即在调节遗传毒物毒性反应方面是“双刃剑”。理解 ncRNA 的“双刃剑”效应对于我们进一步理解环境毒物诱导的人类疾病的发病机制以及构建新的预防和治疗靶点至关重要。此外，ncRNA 及其相互作用以及细胞内下游靶标形成的 MEN 对于考虑外部因素（环境毒物）与内在基因组 ncRNA 之间的主动关系非常重要，无论是抑制还是促进（下调或上调），并且工程 ncRNA 疗法可以抑制或促进环境毒物靶标固有基因组 ncRNA 的表达。此外，MEN 有望应用于环境遗传毒物暴露的全场景水平的机制解释和风险评估。随着分子生物学的快速发展，所提出的 MEN 观点将提供更清晰或更全面的整体观点。
