ABSTRACT

Airborne particulate matter (PM) is a major health hazard worldwide and is a key factor in lung cancer, which remains the most common type of malignancy and the leading cause of cancer-related deaths. DNA methylation is a critical mechanism underlying the detrimental effects of PM, however, the molecular link between PM exposure and lung cancer remains to be elucidated. N-α-acetyltransferase 10 (NAA10) is involved in the cell cycle, migration, apoptosis, differentiation, and proliferation. In order to investigate the role of NAA10 in PM-induced pathogenesis processes leading to lung cancer, we determined the expression and methylation of NAA10 in normal human bronchial epithelial (NHBE) cells treated with PM₁₀, PM₁₀-polycyclic aromatic hydrocarbons (PAH), and PM_2.5 and evaluated the prognostic value of the NAA10 methylation status in lung cancer patients. Exposure to all PM types significantly increased the expression of NAA10 mRNA and decreased the methylation of the NAA10 promoter in NHBE cells compared with the mock-treated control. NAA10 hypomethylation was observed in 9.3% (13/140) of lung cancer tissue samples and correlated with NAA10 transcriptional upregulation. Univariate and multivariate analyses revealed that NAA10 hypomethylation was associated with decreased survival of patients with lung cancer. Therefore, these results suggest that PM-induced hypomethylation of the NAA10 may play an important role in the pathogenesis of lung cancer and may be used as a potential prognostic biomarker for lung cancer progression. Further studies with large numbers of patients are warranted to confirm our findings.

摘要

空气中的颗粒物 (PM) 是全世界的主要健康危害，也是肺癌的关键因素，肺癌仍然是最常见的恶性肿瘤类型，也是癌症相关死亡的主要原因。DNA 甲基化是 PM 有害影响的关键机制，然而，PM 暴露与肺癌之间的分子联系仍有待阐明。N-α-乙酰转移酶 10 (NAA10) 参与细胞周期、迁移、凋亡、分化和增殖。为了研究 NAA10 在 PM 诱导的肺癌发病机制中的作用，我们测定了NAA10在经 PM ₁₀、PM ₁₀处理的正常人支气管上皮 (NHBE) 细胞中的表达和甲基化-多环芳烃 (PAH) 和 PM _{2.5 ，并评估了}NAA10甲基化状态在肺癌患者中的预后价值。与模拟处理的对照相比，暴露于所有 PM 类型显着增加NAA10 mRNA的表达并降低 NHBE 细胞中NAA10启动子的甲基化。在 9.3% (13/140) 的肺癌组织样本中观察到NAA10低甲基化，并与NAA10转录上调相关。单变量和多变量分析显示NAA10低甲基化与肺癌患者的生存率下降有关。因此，这些结果表明，PM 诱导的NAA10低甲基化可能在肺癌的发病机制中发挥重要作用，并可用作肺癌进展的潜在预后生物标志物。需要对大量患者进行进一步研究以证实我们的发现。