Environmental Toxicology Graduate Program, University of California, Riverside, CA, USA.
Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA, USA.
Inhal Toxicol. 2023 May-Jun;35(5-6):157-168. doi: 10.1080/08958378.2023.2185703. Epub 2023 Mar 6.
Exposure to diesel exhaust particles (DEP) has been linked to a variety of adverse health effects, including increased morbidity and mortality from cardiovascular diseases, chronic obstructive pulmonary disease (COPD), metabolic syndrome, and lung cancer. The epigenetic changes caused by air pollution have been associated with increased health risks. However, the exact molecular mechanisms underlying the lncRNA-mediated pathogenesis induced by DEP exposure have not been revealed.
Through RNA-sequencing and integrative analysis of both mRNA and lncRNA profiles, this study investigated the role of lncRNAs in altered gene expression in healthy and diseased human primary epithelial cells (NHBE and DHBE-COPD) exposed to DEP at a dose of 30 μg/cm.
We identified 503 and 563 differentially expressed (DE) mRNAs and a total of 10 and 14 DE lncRNAs in NHBE and DHBE-COPD cells exposed to DEP, respectively. In both NHBE and DHBE-COPD cells, enriched cancer-related pathways were identified at mRNA level, and 3 common lncRNAs and were found to be associated with cancer initiation and progression. In addition, we identified two -acting ( and ) and several -acting lncRNAs (e.g. ) only differentially expressed in COPD cells, which could potentially play a role in carcinogenesis and determine their susceptibility to DEP exposure.
Overall, our work highlights the potential importance of lncRNAs in regulating DEP-induced gene expression changes associated with carcinogenesis, and individuals suffering from COPD are likely to be more vulnerable to these environmental triggers.
接触柴油机排气颗粒（DEP）与多种健康不良影响有关，包括心血管疾病、慢性阻塞性肺疾病（COPD）、代谢综合征和肺癌的发病率和死亡率增加。空气污染引起的表观遗传变化与健康风险增加有关。然而，DEP 暴露引起的长链非编码 RNA（lncRNA）介导的发病机制的确切分子机制尚未揭示。
通过 RNA 测序和 mRNA 和 lncRNA 谱的综合分析，本研究调查了 lncRNA 在暴露于 30μg/cm 的 DEP 时改变健康和患病的人原代上皮细胞（NHBE 和 DHBE-COPD）中基因表达的作用。
我们分别在暴露于 DEP 的 NHBE 和 DHBE-COPD 细胞中鉴定出 503 个和 563 个差异表达（DE）mRNA 和总共 10 个和 14 个 DE lncRNA。在 NHBE 和 DHBE-COPD 细胞中，在 mRNA 水平上都鉴定出富含癌症相关途径，并且发现 3 个共同的 lncRNA 和 与癌症发生和进展有关。此外，我们发现两个双效（和）和几个双效 lncRNA（例如）仅在 COPD 细胞中差异表达，它们可能在致癌作用中发挥作用，并确定它们对 DEP 暴露的敏感性。
总体而言，我们的工作强调了 lncRNA 在调节与致癌作用相关的 DEP 诱导的基因表达变化中的潜在重要性，患有 COPD 的个体可能更容易受到这些环境触发因素的影响。
