Programa de Pós-graduação em Ciências Farmacêuticas, Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil.
Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil.
Mol Biol Rep. 2020 Nov;47(11):9097-9122. doi: 10.1007/s11033-020-05916-3. Epub 2020 Oct 21.
Scientific advances in recent decades have revealed an incredible degree of plasticity in gene expression in response to various environmental, nutritional, physiological, pathological, and behavioral conditions. Epigenetics emerges in this sense, as the link between the internal (genetic) and external (environmental) factors underlying the expression of the phenotype. Methylation of DNA and histone post-translationa modifications are canonical epigenetic events. Additionally, noncoding RNAs molecules (microRNAs and lncRNAs) have also been proposed as another layer of epigenetic regulation. Together, these events are responsible for regulating gene expression throughout life, controlling cellular fate in both normal and pathological development. Despite being a relatively recent science, epigenetics has been arousing the interest of researchers from different segments of the life sciences and the general public. This review highlights the recent advances in the characterization of the epigenetic events and points promising use of these brands for the diagnosis, prognosis, and therapy of diseases. We also present several classes of epigenetic modifying compounds with therapeutic applications (so-call epidrugs) and their current status in clinical trials and approved by the FDA. In summary, hopefully, we provide the reader with theoretical bases for a better understanding of the epigenetic mechanisms and of the promising application of these marks and events in the medical clinic.
近几十年来,科学的进步揭示了基因表达在应对各种环境、营养、生理、病理和行为条件下具有令人难以置信的可塑性。在这个意义上,表观遗传学作为表型表达背后的内部(遗传)和外部(环境)因素之间的联系出现了。DNA 甲基化和组蛋白翻译后修饰是典型的表观遗传事件。此外,非编码 RNA 分子(microRNAs 和 lncRNAs)也被提出作为另一种表观遗传调控层。这些事件共同负责调节整个生命周期的基因表达,控制正常和病理发育中的细胞命运。尽管是一门相对较新的科学,但表观遗传学已经引起了来自生命科学不同领域的研究人员和普通公众的兴趣。这篇综述强调了对表观遗传事件特征的最新进展,并指出了这些标记物在疾病的诊断、预后和治疗中的有前途的应用。我们还介绍了几类具有治疗应用的表观遗传修饰化合物(所谓的 epi 药物)及其在临床试验中的现状和 FDA 批准情况。总之,希望我们为读者提供了更好地理解表观遗传机制和这些标记物和事件在医学临床中的有前途应用的理论基础。