当前位置: X-MOL 学术Semin. Cancer Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Epigenetic deregulation in cancer: Enzyme players and non-coding RNAs
Seminars in Cancer Biology ( IF 12.1 ) Pub Date : 2020-07-30 , DOI: 10.1016/j.semcancer.2020.07.013
Ammad Ahmad Farooqi 1 , Sundas Fayyaz 2 , Palmiro Poltronieri 3 , George Calin 4 , Massimo Mallardo 5
Affiliation  

Data obtained from cutting-edge research have shown that deregulated epigenetic marks are critical hallmarks of cancer. Rapidly emerging scientific evidence has helped in developing a proper understanding of the mechanisms leading to control of cellular functions, from changes in chromatin accessibility, transcription and translation, and in post-translational modifications. Firstly, mechanisms of DNA methylation and demethylation are introduced, as well as modifications of DNA and RNA, with particular focus on N6-methyladenosine (m6A), discussing the effects of these modifications in normal cells and in malignancies. Then, chromatin modifying proteins and remodelling complexes are discussed. Many enzymes and accessory proteins in these complexes have been found mutated or have undergone differential splicing, leading to defective protein complexes. Epigenetic mechanisms acting on nucleosomes by polycomb repressive complexes and on chromatin by SWI/SNF complexes on nucleosome assembly/disassembly, as well as main mutated genes linked to cancers, are reviewed. Among enzymes acting on histones and other proteins erasing the reversible modifications are histone deacetylases (HDACs). Sirtuins are of interest since most of these enzymes not only deacylate histones and other proteins, but also post-translationally modify proteins adding a Mono-ADP-ribose (MAR) moiety. MAR can be read by MACRO-domain containing proteins such as histone MacroH2A1, with specific function in chromatin assembly. Finally, recent advances are presented on non-coding RNAs with a scaffold function, prospecting their role in assembly of chromatin modifying complexes, recruiting enzyme players to chromatin regions. Lastly, the imbalance in metabolites production due to mitochondrial dysfunction is presented, with the potential of these metabolites to inhibit enzymes, either writers, readers or erasers of epitranscriptome marks. In the perspectives, studies are overwied on drugs under development aiming to limit excessive enzyme activities and to reactivate chromatin modifying complexes, for therapeutic application. This knowledge may lead to novel drugs and personalised medicine for cancer patients.



中文翻译:

癌症中的表观遗传失调:酶参与者和非编码 RNA

从前沿研究中获得的数据表明,失调的表观遗传标记是癌症的关键标志。迅速出现的科学证据有助于正确理解导致细胞功能控制的机制,包括染色质可及性、转录和翻译的变化以及翻译后修饰。首先,介绍了 DNA 甲基化和去甲基化的机制,以及 DNA 和 RNA 的修饰,特别关注 N6-甲基腺苷 (m6A),讨论了这些修饰对正常细胞和恶性肿瘤的影响。然后,讨论了染色质修饰蛋白和重塑复合物。已发现这些复合物中的许多酶和辅助蛋白发生突变或经历了差异剪接,导致有缺陷的蛋白质复合物。综述了多梳抑制复合物作用于核小体的表观遗传机制和核小体组装/解体中 SWI/SNF 复合物作用于染色质的表观遗传机制,以及与癌症相关的主要突变基因。作用于组蛋白和其他消除可逆修饰的蛋白质的酶包括组蛋白脱乙酰酶 (HDAC)。Sirtuins 是令人感兴趣的,因为这些酶中的大多数不仅使组蛋白和其他蛋白质脱乙酰化,而且还在翻译后修饰蛋白质,添加单 ADP-核糖 (MAR) 部分。MAR 可以被包含 MACRO 结构域的蛋白质读取,例如组蛋白 MacroH2A1,在染色质组装中具有特定功能。最后,介绍了具有支架功能的非编码 RNA 的最新进展,展望了它们在染色质修饰复合物组装中的作用,将酶参与者招募到染色质区域。最后,提出了由于线粒体功能障碍导致的代谢物产生的不平衡,这些代谢物有可能抑制酶,无论是表观转录组标记的书写者、阅读者还是擦除者。从这些观点来看,正在开发旨在限制过度酶活性和重新激活染色质修饰复合物以用于治疗应用的药物的研究过于繁重。这些知识可能会为癌症患者带来新的药物和个性化药物。对旨在限制过度酶活性和重新激活染色质修饰复合物以用于治疗应用的正在开发的药物进行了过多的研究。这些知识可能会为癌症患者带来新的药物和个性化药物。对旨在限制过度酶活性和重新激活染色质修饰复合物以用于治疗应用的正在开发的药物进行了过多的研究。这些知识可能会为癌症患者带来新的药物和个性化药物。

更新日期:2020-07-30
down
wechat
bug