Environmental Toxicology Graduate Program, University of California, Riverside, California 92521, United States.
Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, United States.
Chem Res Toxicol. 2021 Mar 15;34(3):892-900. doi: 10.1021/acs.chemrestox.0c00516. Epub 2021 Mar 3.
Dimethyl selenide (DMSe) is one of the major volatile organoselenium compounds released into the atmosphere through plant metabolism and microbial methylation. DMSe has been recently revealed as a precursor of secondary organic aerosol (SOA), and its resultant SOA possesses strong oxidizing capability toward thiol groups that can perturb several major biological pathways in human airway epithelial cells and is linked to genotoxicity, DNA damage, and p53-mediated stress responses. Mounting evidence has suggested that long noncoding RNAs (lncRNAs) are involved in stress responses to internal and environmental stimuli. However, the underlying molecular interactions remain to be elucidated. In this study, we performed integrative analyses of lncRNA-mRNA coexpression in the transformed human bronchial epithelial BEAS-2B cell line exposed to DMSe-derived SOA. We identified a total of 971 differentially expressed lncRNAs in BEAS-2B cells exposed to SOA derived from O and OH oxidation of DMSe. Gene ontology (GO) network analysis of -targeted genes showed significant enrichment of DNA damage, apoptosis, and p53-mediated stress response pathways. -Acting lncRNAs, including , , , and , known to be associated with human carcinogenesis, also showed altered expression in cell treated with DMSe-SOA. Overall, this study highlights the regulatory role of lncRNAs in altered gene expression induced by DMSe-SOA exposure.
二甲基硒（DMSe）是通过植物代谢和微生物甲基化释放到大气中的主要挥发性有机硒化合物之一。DMSe 最近被揭示为次生有机气溶胶（SOA）的前体，其产生的 SOA 具有很强的巯基氧化能力，可干扰人呼吸道上皮细胞中的几个主要生物途径，并与遗传毒性、DNA 损伤和 p53 介导的应激反应有关。越来越多的证据表明，长非编码 RNA（lncRNA）参与对内部和环境刺激的应激反应。然而，其潜在的分子相互作用仍有待阐明。在这项研究中，我们对暴露于 DMSe 衍生的 SOA 的转化人支气管上皮 BEAS-2B 细胞系中的 lncRNA-mRNA 共表达进行了综合分析。我们共鉴定了 971 个在 BEAS-2B 细胞中差异表达的 lncRNA，这些细胞暴露于 DMSe 的 O 和 OH 氧化衍生的 SOA 中。对靶基因的基因本体（GO）网络分析显示，DNA 损伤、细胞凋亡和 p53 介导的应激反应途径显著富集。-作用的 lncRNA，包括 、 、 、 ，已知与人类致癌作用有关，在 DMSe-SOA 处理的细胞中也表现出表达改变。总体而言，这项研究强调了 lncRNA 在 DMSe-SOA 暴露诱导的基因表达改变中的调节作用。
