Li Yepeng, Wei Zhongheng, Huang Shiqing, Yang Bo
Department of Oncology, Biomedical Research Center, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi Zhuang Autonomous Region 533000, P.R. China.
Key Laboratory of Guangxi College and Universities, Biomedical Research Center, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi Zhuang Autonomous Region 533000, P.R. China.
Oncol Lett. 2020 Dec;20(6):288. doi: 10.3892/ol.2020.12151. Epub 2020 Sep 23.
Reactive oxygen species, particularly hydrogen peroxide (HO), can induce proliferation inhibition and death of A549 cells via oxidative stress. Oxidative stress has effect on DNA methylation. Oxidative stress and DNA methylation feature a common denominator: The one carbon cycle. To explore the inhibitory mechanism of HO on the proliferation of lung cancer cells, the present study analysed the mRNA expression and methylation profiles in A549 cells treated with HO for 24 h, as adenocarcinoma is the most common pathological type of lung cancer. The DNA methylation profile was constructed using reduced representation bisulphite sequencing, which identified 29,755 differentially methylated sites (15,365 upregulated and 14,390 downregulated), and 1,575 differentially methylated regions located in the gene promoters were identified using the methylKit. Analysis of the assocaition between gene expression and methylation levels revealed that several genes were downregulated and hypermethylated, including cyclin-dependent kinase inhibitor 3, denticleless E3 ubiquitin protein ligase homolog, centromere protein (CENP)F, kinesin family member (KIF)20A, CENPA, KIF11, PCNA clamp-associated factor and GINS complex subunit 2, which may be involved in the inhibitory process of HO on the proliferation of A549 cells.
活性氧，尤其是过氧化氢（H₂O₂），可通过氧化应激诱导A549细胞的增殖抑制和死亡。氧化应激对DNA甲基化有影响。氧化应激和DNA甲基化有一个共同特点：一碳循环。为了探究H₂O₂对肺癌细胞增殖的抑制机制，本研究分析了用H₂O₂处理24小时的A549细胞中的mRNA表达和甲基化谱，因为腺癌是肺癌最常见的病理类型。使用简化代表性亚硫酸氢盐测序构建DNA甲基化谱，该方法鉴定出29,755个差异甲基化位点（15,365个上调和14,390个下调），并使用methylKit鉴定出位于基因启动子中的1,575个差异甲基化区域。基因表达与甲基化水平之间的关联分析表明，几个基因下调且发生高甲基化，包括细胞周期蛋白依赖性激酶抑制剂3、无齿E3泛素蛋白连接酶同源物、着丝粒蛋白（CENP）F、驱动蛋白家族成员（KIF）20A、CENPA、KIF11、PCNA钳相关因子和GINS复合体亚基2，这些基因可能参与了H₂O₂对A549细胞增殖的抑制过程。
