Department of Toxicogenomics, Maastricht University, Maastricht, The Netherlands.
Department of Biobank Research, and Occupational and Environmental Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
Sci Rep. 2017 Aug 23;7(1):9262. doi: 10.1038/s41598-017-10167-7.
Persistent organic pollutants (POPs) are synthetic chemical substances that accumulate in our environment. POPs such as polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB) and dichlorodiphenyltrichloroethane (DDT) have been classified as carcinogenic to humans and animals. Due to their resistance to biodegradation humans are still exposed to these compounds worldwide. We aim to evaluate the miRNA and transcriptomic response of a human population exposed to POPs. The miRNA and transcriptomic response was measured in blood of healthy subjects by microarray technology and associated with the serum concentrations of six PCB congeners, DDE (a common DDT metabolite), and HCB. A total of 93 miRNA levels appeared significantly associated with the POP-exposure (FDR < 0.05). The miRNA profile includes four tumor suppressor miRNAs, namely miR-193a-3p, miR-152, miR-31-5p and miR-34a-5p. Integration of the miRNA profile with the transcriptome profile suggests an interaction with oncogenes such as MYC, CCND1, BCL2 and VEGFA. We have shown that exposure to POPs is associated with human miRNA and transcriptomic responses. The identified miRNAs and target genes are related to various types of cancer and involved in relevant signaling pathways like wnt and p53. Therefore, these miRNAs may have great potential to contribute to biomarker-based environmental health risk assessment.
持久性有机污染物 (POPs) 是在我们的环境中积累的合成化学物质。多氯联苯 (PCBs)、六氯苯 (HCB) 和滴滴涕 (DDT) 等 POP 已被归类为对人类和动物具有致癌性。由于它们不易生物降解,人类仍在全球范围内接触这些化合物。我们旨在评估接触 POP 的人群的 miRNA 和转录组反应。通过微阵列技术测量健康受试者血液中的 miRNA 和转录组反应,并将其与六种 PCB 同系物、DDE(一种常见的 DDT 代谢物)和 HCB 的血清浓度相关联。共有 93 个 miRNA 水平与 POP 暴露呈显著相关(FDR<0.05)。miRNA 谱包括四个肿瘤抑制 miRNA,即 miR-193a-3p、miR-152、miR-31-5p 和 miR-34a-5p。miRNA 谱与转录组谱的整合表明与癌基因如 MYC、CCND1、BCL2 和 VEGFA 相互作用。我们已经表明,接触 POP 与人类 miRNA 和转录组反应有关。鉴定的 miRNAs 和靶基因与各种类型的癌症有关,并参与相关的信号通路,如 wnt 和 p53。因此,这些 miRNA 可能具有很大的潜力为基于生物标志物的环境健康风险评估做出贡献。