Repeated PM2.5 exposure inhibits BEAS-2B cell P53 expression through ROS-Akt-DNMT3B pathway-mediated promoter hypermethylation

作者：Wei Zhou, Dongdong Tian, Jun He, Yimei Wang, Lijun Zhang, Lan Cui, Jia Li, Li Zhang, Lizhong Li, Yulei Shu, Shouzhong Yu, Jun Zhao, Xiaoyan Yuan, Shuangqing Peng · 发表于：Oncotarget · 年份：2016 · DOI：10.18632/oncotarget.7842 · 被引用次数：120 · 研究领域：Epigenetics and DNA Methylation、Air Quality and Health Impacts、Energy and Environment Impacts

// Wei Zhou 1 , Dongdong Tian 1 , Jun He 1 , Yimei Wang 1 , Lijun Zhang 1 , Lan Cui 1 , Li Jia 1 , Li Zhang 1 , Lizhong Li 1 , Yulei Shu 1 , Shouzhong Yu 1 , Jun Zhao 1 , Xiaoyan Yuan 1 , Shuangqing Peng 1 1 Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing 100071, PR China Correspondence to: Xiaoyan Yuan, email: yanziyuan2007@126.com Shuangqing Peng, email: pengsq@hotmail.com Keywords: PM2.5, Akt, DNMT3B, P53, hypermethylation Received: September 30, 2015      Accepted: February 06, 2016      Published: March 02, 2016 ABSTRACT Long-term exposure to fine particulate matter (PM2.5) has been reported to be closely associated with the increased lung cancer risk in populations, but the mechanisms underlying PM-associated carcinogenesis are not yet clear. Previous studies have indicated that aberrant epigenetic alterations, such as genome-wide DNA hypomethylation and gene-specific DNA hypermethylation contribute to lung carcinogenesis. And silence or mutation of P53 tumor suppressor gene is the most prevalent oncogenic driver in lung cancer development. To explore the effects of PM2.5 on global and P53 promoter methylation changes and the mechanisms involved, we exposed human bronchial epithelial cells (BEAS-2B) to low concentrations of PM2.5 for 10 days. Our results indicated that PM2.5-induced global DNA hypomethylation was accompanied by redu...