癌症DNA甲基化改变的分析和治疗概况;染色质排列的变化和组蛋白表面的变化综述。

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Accounts of Chemical Research Pub Date : 2023-02-17 eCollection Date: 2023-09-01 DOI:10.1515/hmbci-2022-0043
Seyedeh Elham Norollahi, Sogand Vahidi, Shima Shams, Arman Keymoradzdeh, Armin Soleymanpour, Nazanin Solymanmanesh, Ebrahim Mirzajani, Vida Baloui Jamkhaneh, Ali Akbar Samadani
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引用次数: 0

摘要

DNA甲基化是激活基因转录抑制的最重要的表观遗传学元件,并参与所有类型恶性肿瘤的发病机制。值得注意的是,DNA甲基化的效应物是DNMT(DNA甲基转移酶),它在DNA复制过程后催化半甲基化DNA的从头甲基化或保持甲基化。癌症的DNA甲基化结构发生了改变,DNA甲基化有助于癌症的发展,包括直接突变、癌症基因组的低甲基化和TSG(肿瘤抑制基因)启动子的局部高甲基化。显而易见,DNA甲基化,核小体重塑,RNA介导的靶向,组蛋白修饰平衡调节许多生物学活性,这些活性对癌症的发生是必不可少的,也可以影响许多表观遗传学变化,包括DNA甲基化和组蛋白修饰,以及在预防和治疗许多癌症中调节非编码miRNA的表达。表观遗传学指出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组成,结合在由一个H3/H4四聚体和两个H2A/H2B二聚体组成的组蛋白八聚体周围。DNA甲基化优先分布在核小体区域,而在侧翼核小体缺失的DNA上增加较少,这意味着核小体定位和DNA甲基化之间存在联系。在致癌过程中,表观基因组的畸变也可能包括耐药性的进展。在本报告中,我们报道了这些表观遗传信号通路背后的基本注释,并强调了在癌症中可以得出其失调结论的证据。这些发现与表观遗传学药物对抗染色质调节因子观察到的有希望的临床前和临床结果相结合,证实了表观遗传学在癌症治疗中的重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Analytical and therapeutic profiles of DNA methylation alterations in cancer; an overview of changes in chromatin arrangement and alterations in histone surfaces.

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 de novo 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.

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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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