NAA10 Hypomethylation is associated with particulate matter exposure and worse prognosis for patients with non-small cell lung cancer

다국어 초록 (Multilingual Abstract)

Airborne particulate matter (PM) is a major health hazard worldwide and is a key factor in lungcancer, which remains the most common type of malignancy and the leading cause of cancerrelateddeaths. 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 pathogenesisprocesses leading to lung cancer, we determined the expression and methylation of NAA10 innormal human bronchial epithelial (NHBE) cells treated with PM10, PM10-polycyclic aromatichydrocarbons (PAH), and PM2.5 and evaluated the prognostic value of the NAA10 methylationstatus in lung cancer patients. Exposure to all PM types significantly increased the expressionof NAA10 mRNA and decreased the methylation of the NAA10 promoter in NHBE cellscompared 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 associatedwith decreased survival of patients with lung cancer. Therefore, these results suggest that PMinducedhypomethylation of the NAA10 may play an important role in the pathogenesis oflung cancer and may be used as a potential prognostic biomarker for lung cancerprogression. Further studies with large numbers of patients are warranted to confirm ourfindings.