Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.
Environ Mol Mutagen. 2023 Mar;64(3):159-166. doi: 10.1002/em.22533. Epub 2023 Mar 1.
Diesel engine exhaust (DEE) is an established lung carcinogen, but the biological mechanisms of diesel-induced lung carcinogenesis are not well understood. MicroRNAs (miRNAs) are small noncoding RNAs that play a potentially important role in regulating gene expression related to lung cancer. We conducted a cross-sectional molecular epidemiology study to evaluate whether serum levels of miRNAs are altered in healthy workers occupationally exposed to DEE compared to unexposed controls. We conducted a two-stage study, first measuring 405 miRNAs in a pilot study of six DEE-exposed workers exposed and six controls. In the second stage, 44 selected miRNAs were measured using the Fireplex circulating miRNA assay that profiles miRNAs directly from biofluids of 45 workers exposed to a range of DEE (Elemental Carbon (EC), median, range: 47.7, 6.1-79.7 μg/m ) and 46 controls. The relationship between exposure to DEE and EC with miRNA levels was analyzed using linear regression adjusted for potential confounders. Serum levels of four miRNAs were significantly lower (miR-191-5p, miR-93-5p, miR-423-3p, miR-122-5p) and one miRNA was significantly higher (miR-92a-3p) in DEE exposed workers compared to controls. Of these miRNAs, miR-191-5p (p = .001, FDR = 0.04) and miR-93-5p (p = .009, FDR = 0.18) showed evidence of an inverse exposure-response with increasing EC levels. Our findings suggest that occupational exposure to DEE may affect circulating miRNAs implicated in biological processes related to carcinogenesis, including immune function.
柴油机废气（DEE）是一种已确定的肺癌致癌物，但柴油机诱导肺癌发生的生物学机制尚不清楚。microRNAs（miRNAs）是一种小的非编码 RNA，在调节与肺癌相关的基因表达方面可能发挥着重要作用。我们进行了一项横断面分子流行病学研究，以评估与未接触对照相比，职业性接触 DEE 的健康工人血清中 miRNA 水平是否发生改变。我们进行了两阶段研究，首先在六名接触 DEE 的暴露工人和六名对照的试点研究中测量了 405 种 miRNA。在第二阶段，使用 Fireplex 循环 miRNA 分析方法测量了 44 种选定的 miRNA，该方法可直接从暴露于不同范围 DEE（元素碳（EC），中位数，范围：47.7，6.1-79.7μg/m ）的 45 名工人和 46 名对照的生物流体中分析 miRNA 图谱。使用线性回归分析调整潜在混杂因素后，分析了 DEE 和 EC 暴露与 miRNA 水平之间的关系。与对照组相比，DEE 暴露工人的四种 miRNA 血清水平明显降低（miR-191-5p、miR-93-5p、miR-423-3p、miR-122-5p），一种 miRNA 水平明显升高（miR-92a-3p）。在这些 miRNA 中，miR-191-5p（p = 0.001，FDR = 0.04）和 miR-93-5p（p = 0.009，FDR = 0.18）表现出与 EC 水平呈反向暴露-反应关系的证据。我们的研究结果表明，职业性接触 DEE 可能会影响与致癌作用相关的生物过程中涉及的循环 miRNA，包括免疫功能。
