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表观遗传学和 epi-miRNAs:白血病的潜在标志物/治疗靶点。

Epigenetics and Epi-miRNAs: Potential markers/therapeutics in leukemia.

机构信息

Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.

Department of Genetics and Molecular Medicine, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.

出版信息

Biomed Pharmacother. 2018 Oct;106:1668-1677. doi: 10.1016/j.biopha.2018.07.133. Epub 2018 Jul 29.

Abstract

Epigenetic variations can play remarkable roles in different normal and abnormal situations. Such variations have been shown to have a direct role in the pathogenesis of various diseases either through inhibition of tumor suppressor genes or increasing the expression of oncogenes. Enzymes involving in epigenetic machinery are the main actors in tuning the epigenetic-based controls on gene expressions. Aberrant expression of these enzymes can trigger a big chaos in the cellular gene expression networks and finally lead to cancer progression. This situation has been shown in different types of leukemia, where high or low levels of an epigenetic enzyme are partly or highly responsible for involvement or progression of a disease. DNA hypermethylation, different histone modifications, and aberrant miRNA expressions are three main epigenetic variations, which have been shown to play a role in leukemia progression. Epigenetic based treatments now are considered as novel and effective therapies in order to decrease the abnormal epigenetic modifications in patient cells. Different epigenetic-based approaches have been developed and tested to inhibit or reverse the unusual expression of epigenetic agents in leukemia. The reciprocal behavior of miRNAs in the regulation of epigenetic modifiers, while being regulated by them, unlocks a new opportunity in order to design some epigenetic-based miRNAs able to silence or sensitize these effectors in leukemia.

摘要

表观遗传变异在不同的正常和异常情况下都可以发挥显著作用。这些变异已被证明通过抑制肿瘤抑制基因或增加癌基因的表达而直接参与各种疾病的发病机制。涉及表观遗传机制的酶是调节基于表观遗传的基因表达控制的主要因素。这些酶的异常表达会引发细胞基因表达网络的巨大混乱,最终导致癌症的进展。这种情况在不同类型的白血病中已经得到证实,其中表观遗传酶的高或低水平部分或高度负责疾病的参与或进展。DNA 高甲基化、不同的组蛋白修饰和异常的 miRNA 表达是三种主要的表观遗传变异,它们已被证明在白血病进展中发挥作用。基于表观遗传的治疗现在被认为是一种新颖有效的治疗方法,以减少患者细胞中异常的表观遗传修饰。已经开发和测试了不同的基于表观遗传的方法来抑制或逆转白血病中表观遗传剂的异常表达。miRNA 在表观遗传修饰物调节中的相互作用,同时受其调节,为设计能够沉默或敏化白血病中这些效应物的基于表观遗传的 miRNA 提供了一个新的机会。

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