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DNA低甲基化与颗粒物暴露以及非小细胞肺癌患者的不良预后相关。

Hypomethylation is associated with particulate matter exposure and worse prognosis for patients with non-small cell lung cancer.

作者信息

Lee Ji Yun, Lee Su Man, Lee Won Kee, Park Jae Yong, Kim Dong Sun

机构信息

Department of Anatomy, BK21 Plus Biomedical Convergence Program, Daegu, Republic of Korea.

Department of Graduate School for Biomedical Science & Engineering, Hanyang University, Seoul, Republic of Korea.

出版信息

Anim Cells Syst (Seoul). 2023 Apr 4;27(1):72-82. doi: 10.1080/19768354.2023.2189934. eCollection 2023.

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 in normal human bronchial epithelial (NHBE) cells treated with PM, PM-polycyclic aromatic hydrocarbons (PAH), and PM and evaluated the prognostic value of the methylation status in lung cancer patients. Exposure to all PM types significantly increased the expression of mRNA and decreased the methylation of the promoter in NHBE cells compared with the mock-treated control. hypomethylation was observed in 9.3% (13/140) of lung cancer tissue samples and correlated with transcriptional upregulation. Univariate and multivariate analyses revealed that hypomethylation was associated with decreased survival of patients with lung cancer. Therefore, these results suggest that PM-induced hypomethylation of the 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)是全球主要的健康危害因素,是肺癌的关键因素,肺癌仍是最常见的恶性肿瘤类型和癌症相关死亡的主要原因。DNA甲基化是PM产生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诱导的导致肺癌的发病过程中的作用,我们测定了用PM、PM-多环芳烃(PAH)处理的正常人支气管上皮(NHBE)细胞中NAA10的表达和甲基化情况,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,暴露于所有类型的PM均显著增加了NHBE细胞中NAA10 mRNA的表达,并降低了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,且与NAA10转录上调相关。单因素和多因素分析显示,NAA10低甲基化与肺癌患者生存率降低有关。因此,这些结果表明,PM诱导的NAA10低甲基化可能在肺癌发病机制中起重要作用,并可能作为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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f125/10075488/5ff77f9efd02/TACS_A_2189934_F0001_OB.jpg

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