Cancer Research Center and Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran.
Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Horm Mol Biol Clin Investig. 2023 Feb 17;44(3):337-356. doi: 10.1515/hmbci-2022-0043. eCollection 2023 Sep 1.
DNA methylation is the most important epigenetic element that activates the inhibition of gene transcription and is included in the pathogenesis of all types of malignancies. Remarkably, the effectors of DNA methylation are DNMTs (DNA methyltransferases) that catalyze or keep methylation of hemimethylated DNA after the DNA replication process. DNA methylation structures in cancer are altered, with three procedures by which DNA methylation helps cancer development which are including direct mutagenesis, hypomethylation of the cancer genome, and also focal hypermethylation of the promoters of TSGs (tumor suppressor genes). Conspicuously, DNA methylation, nucleosome remodeling, RNA-mediated targeting, and histone modification balance modulate many biological activities that are essential and indispensable to the genesis of cancer and also can impact many epigenetic changes including DNA methylation and histone modifications as well as adjusting of non-coding miRNAs expression in prevention and treatment of many cancers. Epigenetics points to heritable modifications in gene expression that do not comprise alterations in the DNA sequence. The nucleosome is the basic unit of chromatin, consisting of 147 base pairs (bp) of DNA bound around a histone octamer comprised of one H3/H4 tetramer and two H2A/H2B dimers. DNA methylation is preferentially distributed over nucleosome regions and is less increased over flanking nucleosome-depleted DNA, implying a connection between nucleosome positioning and DNA methylation. In carcinogenesis, aberrations in the epigenome may also include in the progression of drug resistance. In this report, we report the rudimentary notes behind these epigenetic signaling pathways and emphasize the proofs recommending that their misregulation can conclude in cancer. These findings in conjunction with the promising preclinical and clinical consequences observed with epigenetic drugs against chromatin regulators, confirm the important role of epigenetics in cancer therapy.
DNA 甲基化是最重要的表观遗传因素，可激活基因转录的抑制作用，并包含在所有类型恶性肿瘤的发病机制中。值得注意的是，DNA 甲基化的效应物是 DNMTs（DNA 甲基转移酶），它们在 DNA 复制过程后催化或保持半甲基化 DNA 的甲基化。在癌症中，DNA 甲基化结构发生改变，DNA 甲基化有三种促进癌症发展的机制，包括直接突变、肿瘤基因组的低甲基化以及 TSG（肿瘤抑制基因）启动子的局灶性高甲基化。显然，DNA 甲基化、核小体重塑、RNA 介导的靶向作用和组蛋白修饰平衡调节许多生物学活性，这些活性对于癌症的发生是必不可少的，并且可以影响许多表观遗传变化，包括 DNA 甲基化和组蛋白修饰以及调节非编码 miRNA 表达，从而预防和治疗许多癌症。表观遗传学是指基因表达的可遗传修饰，不包括 DNA 序列的改变。核小体是染色质的基本单位，由 147 个碱基对 (bp) 的 DNA 围绕由一个 H3/H4 四聚体和两个 H2A/H2B 二聚体组成的组蛋白八聚体组成。DNA 甲基化优先分布在核小体区域，在侧翼核小体缺失 DNA 上的增加较少，这表明核小体定位与 DNA 甲基化之间存在联系。在致癌作用中，表观基因组的异常也可能包括在耐药性的进展中。在本报告中，我们报告了这些表观遗传信号通路背后的基本说明，并强调了证明这些通路的失调可能导致癌症的证据。这些发现结合了针对染色质调节剂的表观遗传药物的有前途的临床前和临床结果，证实了表观遗传学在癌症治疗中的重要作用。
