Department of Biochemistry, Biophysics and Molecular Biology, University of Minnesota-Twin Cities, Minneapolis, MN 55455, USA.
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota-Twin Cities, Minneapolis, MN 55455, USA.
Int J Mol Sci. 2024 Aug 29;25(17):9365. doi: 10.3390/ijms25179365.
Lung cancer remains a major contributor to cancer fatalities, with cigarette smoking known to be responsible for up to 80% of cases. Based on the ability of cigarette smoke to induce inflammation in the lungs and increased lung cancer incidence in smokers with inflammatory conditions such as COPD, we hypothesized that inflammation plays an important role in the carcinogenicity of cigarette smoke. To test this hypothesis, we performed multi-omic analyses of Type II pneumocytes of A/J mice exposed to cigarette smoke for various time periods. We found that cigarette smoke exposure resulted in significant changes in DNA methylation and hydroxymethylation, gene expression patterns, and protein abundance that were partially reversible and contributed to an inflammatory and potentially oncogenic phenotype.
肺癌仍是癌症死亡的主要原因，已知吸烟导致 80%的病例。基于香烟烟雾在肺部引起炎症的能力，以及在患有 COPD 等炎症性疾病的吸烟者中增加肺癌发病率，我们假设炎症在香烟烟雾的致癌作用中起重要作用。为了验证这一假设，我们对 A/J 小鼠的 II 型肺泡细胞进行了多组学分析，这些小鼠暴露于香烟烟雾中不同时间。我们发现，香烟烟雾暴露导致 DNA 甲基化和羟甲基化、基因表达模式和蛋白质丰度发生显著变化，这些变化部分是可逆的，并导致炎症和潜在致癌表型。
