Wang Yihan, Zhang Jingyu, Xiao Xingjun, Liu Hongbo, Wang Fang, Li Song, Wen Yanhua, Wei Yanjun, Su Jianzhong, Zhang Yunming, Zhang Yan
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Department of Gerontology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
Sci Rep. 2016 Mar 7;6:22722. doi: 10.1038/srep22722.
As one of the most widely studied epigenetic modifications, DNA methylation has an important influence on human traits and cancers. Dynamic variations in DNA methylation have been reported in malignant neoplasm and aging; however, the mechanisms remain poorly understood. By constructing an age-associated and cancer-related weighted network (ACWN) based on the correlation of the methylation level and the protein-protein interaction, we found that DNA methylation changes associated with age were closely related to the occurrence of cancer. Additional analysis of 102 module genes mined from the ACWN revealed discrimination based on two main patterns. One pattern involved methylation levels that increased with aging and were higher in cancer patients compared with normal controls (HH pattern). The other pattern involved methylation levels that decreased with aging and were lower in cancer compared with normal (LL pattern). Upon incorporation with gene expression levels, 25 genes were filtered based on negative regulation by DNA methylation. These genes were regarded as potential cancer risk markers that were influenced by age in the process of carcinogenesis. Our results will facilitate further studies regarding the impact of the epigenetic effects of aging on diseases and will aid in the development of tailored cancer preventive strategies.
作为研究最广泛的表观遗传修饰之一，DNA甲基化对人类性状和癌症有重要影响。恶性肿瘤和衰老过程中已报道了DNA甲基化的动态变化；然而，其机制仍知之甚少。通过基于甲基化水平与蛋白质-蛋白质相互作用的相关性构建一个与年龄相关和癌症相关的加权网络（ACWN），我们发现与年龄相关的DNA甲基化变化与癌症的发生密切相关。对从ACWN中挖掘出的102个模块基因的进一步分析揭示了基于两种主要模式的差异。一种模式涉及随着年龄增长而增加且癌症患者中高于正常对照的甲基化水平（HH模式）。另一种模式涉及随着年龄增长而降低且癌症中低于正常水平的甲基化水平（LL模式）。结合基因表达水平，基于DNA甲基化的负调控筛选出25个基因。这些基因被视为在致癌过程中受年龄影响的潜在癌症风险标志物。我们的结果将有助于进一步研究衰老的表观遗传效应对疾病的影响，并有助于制定针对性的癌症预防策略。
