Double-edged effects of noncoding RNAs in responses to environmental genotoxic insults: Perspectives with regards to molecule-ecology network

Abstract 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.