Liang Gangning, Weisenberger Daniel J
a Department of Urology , University of Southern California, USC Norris Comprehensive Cancer Center , Los Angeles , CA , USA.
b Department of Biochemistry and Molecular Medicine , University of Southern California, USC Norris Comprehensive Cancer Center , Los Angeles , CA , USA.
Epigenetics. 2017 Jun 3;12(6):416-432. doi: 10.1080/15592294.2017.1311434. Epub 2017 Mar 30.
DNA methylation aberrancies are hallmarks of human cancers and are characterized by global DNA hypomethylation of repetitive elements and non-CpG rich regions concomitant with locus-specific DNA hypermethylation. DNA methylation changes may result in altered gene expression profiles, most notably the silencing of tumor suppressors, microRNAs, endogenous retorviruses and tumor antigens due to promoter DNA hypermethylation, as well as oncogene upregulation due to gene-body DNA hypermethylation. Here, we review DNA methylation aberrancies in human cancers, their use in cancer surveillance and the interplay between DNA methylation and histone modifications in gene regulation. We also summarize DNA methylation inhibitors and their therapeutic effects in cancer treatment. In this context, we describe the integration of DNA methylation inhibitors with conventional chemotherapies, DNA repair inhibitors and immune-based therapies, to bring the epigenome closer to its normal state and increase sensitivity to other therapeutic agents to improve patient outcome and survival.
DNA甲基化异常是人类癌症的标志，其特征是重复元件和非富含CpG区域的全基因组DNA低甲基化，同时伴有位点特异性DNA高甲基化。DNA甲基化变化可能导致基因表达谱改变，最显著的是由于启动子DNA高甲基化导致肿瘤抑制因子、微小RNA、内源性逆转录病毒和肿瘤抗原沉默，以及由于基因体DNA高甲基化导致癌基因上调。在这里，我们综述了人类癌症中的DNA甲基化异常、它们在癌症监测中的应用以及DNA甲基化与组蛋白修饰在基因调控中的相互作用。我们还总结了DNA甲基化抑制剂及其在癌症治疗中的治疗效果。在此背景下，我们描述了DNA甲基化抑制剂与传统化疗、DNA修复抑制剂和免疫疗法的联合应用，以使表观基因组更接近其正常状态，并增加对其他治疗药物的敏感性，从而改善患者的预后和生存率。
