title: TRIM36 hypermethylation is involved in polycyclic aromatic hydrocarbons-induced cell transformation.
abstract: Long term exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the increasing risk of lung cancer. To identify differentially hypermethylated genes associated with PAHs-induced carcinogenicity, we performed genome-wide DNA methylation analysis in 20 μM benzo(a)pyrene (BaP)-transformed human bronchial epithelial (HBE) cells at different stages of cell transformation. Several methylated genes (CNGA4, FLT1, GAREM1, SFMBT2, TRIM36) were differentially hypermethylated and their mRNA was suppressed in cells at both pre-transformed and transformed stages. Similar results were observed in HBE cells transformed by 20 μg/mL coke oven emissions (COEs) mixture collected from a coking manufacturing facility. In particular, hypermethylation of TRIM36 and suppression of TRIM36 expression were gradually enhanced over the time of COEs treatment. We developed bisulfite pyrosequencing assay and assessed TRIM36 methylation quantitatively. We found that hypermethylation of TRIM36 and reduced gene expression was prevalent in several types of human cancers. TRIM36 hypermethylation appeared in 90.0% (23/30) of Non-Small Cell Lung Cancer (NSCLCs) tissues compared to their paired adjacent tissues with an average increase of 1.32 fold. Furthermore, an increased methylation rate (5.90% v.s 7.38%) and reduced levels of TRIM36 mRNA were found in peripheral lymphocytes (PBLCs) of 151 COEs-exposed workers. In all subjects, TRIM36 hypermethylation was positively correlated with the level of urinary 1-hydroxypyrene (P < 0.001), an internal exposure marker of PAHs, and the DNA damage (P = 0.013). These findings suggest that aberrant hypermethylation of TRIM36 might be involved in the acquisition of malignant phenotype and could be served as a biomarker for risk assessment of PAHs exposure.
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhini
authors.initials: Z
authors.lastname: He
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
authors.forename: Daochuan
authors.initials: D
authors.lastname: Li
authors.affiliation: Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Junxiang
authors.initials: J
authors.lastname: Ma
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Chen
authors.affiliation: Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Huawei
authors.initials: H
authors.lastname: Duan
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Gao
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Xing
authors.affiliation: Department of Thoracic Surgery, The Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
authors.forename: Fangping
authors.initials: F
authors.lastname: Wang
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
authors.forename: Huiyao
authors.initials: H
authors.lastname: Li
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Chen
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China; Department of Thoracic Surgery, The Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, China. Electronic address: chenwen@mail.sysu.edu.cn.
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D001564:Benzo(a)pyrene / Q000032:analysis; D015415:Biomarkers / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced; D003077:Coke; D004249:DNA Damage; D019175:DNA Methylation; D006801:Humans; D016273:Occupational Exposure / Q000032:analysis; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D011721:Pyrenes / Q000652:urine; D013447:Sulfites; D044767:Ubiquitin-Protein Ligases; D000070584:Tripartite Motif Proteins
chemical_list: D000393:Air Pollutants; D001564:Benzo(a)pyrene; D015415:Biomarkers; D002352:Carrier Proteins; D003077:Coke; D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; D013447:Sulfites; C488674:TRIM36 protein, human; D044767:Ubiquitin-Protein Ligases; D000070584:Tripartite Motif Proteins; C033146:1-hydroxypyrene; C042345:hydrogen sulfite
keywords: Cancer biomarkers; Cell transformation; DNA methylation; Human bronchial epithelial cells; Occupational PAHs exposure; Polycyclic aromatic hydrocarbons (PAHs)