H2O2对A549细胞增殖抑制机制的mRNA表达及DNA甲基化分析

2019年10月，右江民族医学院附属医院肿瘤科广西高等学校重点实验室生物医学研究中心(Department of Oncology, 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) YEPENG LI老师研究团队在《Oncology Letters》上发表论文：

“mRNA expression and DNA methylation analysis of the inhibitory mechanism of H₂O₂ on the proliferation of A549 cells”

“H₂O₂对A549细胞增殖抑制机制的mRNA表达及DNA甲基化分析”

Abstract：

Reactive oxygen species, particularly hydrogen peroxide (H2O2), 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 H2O2 on the proliferation of lung cancer cells, the present study analysed the mRNA expression and methylation profiles in A549 cells treated with H2O2 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 H2O2 on the proliferation of A549 cells.

摘要：

活性氧，特别是过氧化氢(H2O2)可通过氧化应激诱导A549细胞增殖抑制和死亡。氧化应激对DNA甲基化有影响。氧化应激和DNA甲基化有一个共同点:一碳循环。为了探讨H2O2对肺癌细胞增殖的抑制机制，本研究分析了H2O2处理A549细胞24 h的mRNA表达和甲基化谱，因为腺癌是肺癌最常见的病理类型。DNA甲基化谱使用减少代表性亚硫酸盐测序构建，鉴定了29,755个差异甲基化位点(15,365个上调，14,390个下调)，并使用methylKit鉴定了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的相关性分析显示，细胞周期蛋白依赖性激酶抑制剂3、无牙E3泛素蛋白连接酶同源物、着丝粒蛋白(CENP)F、激酶家族成员(KIF)20A、CENPA、KIF11、PCNA钳相关因子和GINS复合物亚基2等基因下调和高甲基化，可能参与H2O2对A549细胞增殖的抑制过程。

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