Gao Chen, He Zhini, Li Jie, Li Xiao, Bai Qing, Zhang Zhengbao, Zhang Xiao, Wang Shan, Xiao Xinhua, Wang Fangping, Yan Yan, Li Daochuan, Chen Liping, Zeng Xiaowen, Xiao Yongmei, Dong Guanghui, Zheng Yuxin, Wang Qing, Chen Wen
Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.
Toxicol Rep. 2016 Jan 4;3:160-166. doi: 10.1016/j.toxrep.2015.12.011. eCollection 2016.
To explore whether the alteration of lncRNA expression is correlated with polycyclic aromatic hydrocarbons (PAHs) exposure and DNA damage, we examined PAHs external and internal exposure, DNA damage and lncRNAs (HOTAIR, MALAT1, TUG1 and GAS5) expression in peripheral blood lymphocytes (PBLCs) of 150 male coke oven workers and 60 non-PAHs exposure workers. We found the expression of HOTAIR, MALAT1, and TUG1 were enhanced in PBLCs of coke oven workers and positively correlated with the levels of external PAHs exposure (adjusted < 0.001 for HOTAIR and MALAT1, adjusted = 0.006 for TUG1). However, only HOTAIR and MALAT1 were significantly associated with the level of internal PAHs exposure (urinary 1-hydroxypyrene) with adjusted = 0.298, = 0.024 for HOTAIR and = 0.090, = 0.034 for MALAT1. In addition, the degree of DNA damage was positively associated with MALAT1 and HOTAIR expression in PBLCs of all subjects (adjusted = 0.024, = 0.002 for HOTAIR and = 0.007, = 0.003 for MALAT1). Moreover, we revealed that the global histone 3 lysine 27 trimethylation (H3K27me3) modification was positively associated with the degree of genetic damage (= 0.061, < 0.001) and the increase of HOTAIR expression (= 0.385, = 0.018). Taken together, our findings suggest that altered HOTAIR and MALAT1 expression might be involved in response to PAHs-induced DNA damage.
为探究长链非编码RNA（lncRNA）表达改变是否与多环芳烃（PAHs）暴露及DNA损伤相关，我们检测了150名男性焦炉工人和60名非PAHs暴露工人外周血淋巴细胞（PBLCs）中的PAHs外暴露和内暴露、DNA损伤以及lncRNAs（HOTAIR、MALAT1、TUG1和GAS5）的表达。我们发现，焦炉工人PBLCs中HOTAIR、MALAT1和TUG1的表达增强，且与外源性PAHs暴露水平呈正相关（HOTAIR和MALAT1校正后<0.001，TUG1校正后=0.006）。然而，仅HOTAIR和MALAT1与内源性PAHs暴露水平（尿中1-羟基芘）显著相关，HOTAIR校正后=0.298，=0.024；MALAT1校正后=0.090，=0.034。此外，所有受试者PBLCs中的DNA损伤程度与MALAT1和HOTAIR表达呈正相关（HOTAIR校正后=0.024，=0.002；MALAT1校正后=0.007，=0.003）。而且，我们发现整体组蛋白3赖氨酸27三甲基化（H3K27me3）修饰与遗传损伤程度（=0.061，<0.001）及HOTAIR表达增加（=0.385，=0.018）呈正相关。综上所述，我们的研究结果表明，HOTAIR和MALAT1表达改变可能参与了PAHs诱导的DNA损伤反应。
