Gutiérrez Jorseth Rodelo, Salgado Arturo René Mendoza, Arias Marcio De Ávila, San-Juan-Vergara Homero, Rada Wendy Rosales, Gómez Carlos Mario Meléndez
Organic and Biomedical Chemistry Research Group, Faculty of Basic Sciences, Universidad del Atlántico, Barranquilla, Colombia.
Department of Medicine, Biotechnology Research Group, Health Sciences Division, Universidad del Norte, Barranquilla, Colombia.
Curr Med Chem. 2022;29(9):1503-1542. doi: 10.2174/0929867329666211228111036.
DNA is packaged in an octamer of histones, forming chromatin, a complex of DNA and proteins. The structural matrix of a chromosome, chromatin and its changes are now regarded as important factors in controlling gene expression, which has sparked a lot of interest in understanding genetic pathways governing various diseases, including cancer. DNA methylation in the CpG dinucleotide as a transcriptional silencing mechanism, post-translational histone modifications such as acetylation, methylation, and others that affect chromatin structure, ATP-dependent chromatin remodelling, and miRNA-mediated gene silencing are all found to be important in various types of cancer. In this review, we analyze the main alterations in gene expression, epigenetic modification patterns in cancer cells, the main modulators and inhibitors of each epigenetic mechanism, and the molecular evolution of the most representative inhibitors, all of which point to a promising future for HAT, HDAC, non-glycoside DNMT inhibitors, and domain inhibitors.
DNA被包装在组蛋白八聚体中，形成染色质，即DNA与蛋白质的复合物。染色体的结构基质、染色质及其变化现在被视为控制基因表达的重要因素，这引发了人们对理解调控包括癌症在内的各种疾病的遗传途径的浓厚兴趣。作为一种转录沉默机制，CpG二核苷酸中的DNA甲基化、影响染色质结构的翻译后组蛋白修饰（如乙酰化、甲基化等）、ATP依赖的染色质重塑以及miRNA介导的基因沉默在各类癌症中均被发现具有重要作用。在本综述中，我们分析了基因表达的主要变化、癌细胞中的表观遗传修饰模式、每种表观遗传机制的主要调节剂和抑制剂，以及最具代表性抑制剂的分子进化，所有这些都表明组蛋白乙酰转移酶（HAT）、组蛋白去乙酰化酶（HDAC）、非糖苷DNA甲基转移酶（DNMT）抑制剂和结构域抑制剂有着广阔的前景。
