TRIM36 hypermethylation is involved in polycyclic aromatic hydrocarbons-induced cell transformation
TRIM36 hypermethylation is involved in polycyclic aromatic hydrocarbons-induced cell transformation
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TRIM36高甲基化参与多环芳烃诱导的细胞转化
DOI：
10.1016/j.envpol.2017.03.001
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发表时间：
2017-06-01
影响因子：
8.9
通讯作者：
Chen, Wen
中科院分区：
文献类型：
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作者：
He, Zhini;Li, Daochuan;Chen, Wen
长期接触多环芳烃(PAHs)会增加患肺癌的风险。为了确定与多环芳烃致癌相关的差异高甲基化基因，我们对20亩M苯并(A)芘(BaP)转化的人支气管上皮(HBE)细胞在细胞转化的不同阶段进行了全基因组DNA甲基化分析。几个甲基化基因(CNGA4、Flt1、GAREMI、SFMBT2、TR1M36)在转化前和转化后的细胞中差异甲基化，它们的mRNA在转化前和转化阶段都受到抑制。从焦化制造厂收集的20}微克/毫升焦炉废气(COE)混合物转化的HBE细胞中也观察到了类似的结果。特别是，随着COE5处理时间的延长，TRIM36的高甲基化和对TRIM36表达的抑制逐渐增强。我们建立了亚硫酸氢盐焦磷酸测序方法，并对TRIM36甲基化进行了定量评估。我们发现，TRIM36基因高甲基化和基因表达降低在几种类型的人类癌症中普遍存在。90.0%(23/30)的非小细胞肺癌组织中存在TRIM36高甲基化，与其配对的癌旁组织相比，平均高达1.32倍。此外，151名作业工人的外周血淋巴细胞(PBLCs)甲基化水平升高(5.90%vs.7.38%)，TR1M36基因表达水平降低。在所有受试者中，TRIM36基因高甲基化与尿中多环芳烃内暴露标志物1-羟基芘(P<；0.001)水平及DNA损伤程度呈正相关(P=0.013)。这些发现提示，TR1M36的异常高甲基化可能与恶性表型的获得有关，并可作为多环芳烃暴露风险评估的生物标志物。(C)2017爱思唯尔有限公司。保留所有权利。
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 mu M benzo(a)pyrene (BaP)-transformed human bronchial epithelial (HBE) cells at different stages of cell transformation. Several methylated genes (CNGA4, FLT1, GAREMI, SFMBT2, TR1M36) 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}mu g/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 COE5 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 TR1M36 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 TR1M36 might be involved in the acquisition of malignant phenotype and could be served as a biomarker for risk assessment of PAHs exposure. (C) 2017 Elsevier Ltd. All rights reserved.