人类癌症中epi- mirna对DNA甲基化机制的调控:癌症治疗中出现的新靶点
Regulation of DNA methylation machinery by epi-miRNAs in human cancer: emerging new targets in cancer therapy
原文发布日期:2020-08-10
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Disruption in DNA methylation processes can lead to alteration in gene expression and function that would ultimately result in malignant transformation. In this way, studies have shown that, in cancers, methylation-associated silencing inactivates tumor suppressor genes, as effectively as mutations. DNA methylation machinery is composed of several genes, including those with DNA methyltransferases activity, proteins that bind to methylated cytosine in the promoter region, and enzymes with demethylase activity. Based on a prominent body of evidence, DNA methylation machinery could be regulated by microRNAs (miRNAs) called epi-miRNAs. Numerous studies demonstrated that dysregulation in DNA methylation regulators like upstream epi-miRNAs is indispensable for carcinogenesis; consequently, the malignant capacity of these cells could be reversed by restoring of this regulatory system in cancer. Conceivably, recognition of these epi-miRNAs in cancer cells could not only reveal novel molecular entities in carcinogenesis, but also render promising targets for cancer therapy. In this review, at first, we have an overview of the methylation alteration in cancers, and the effect of this phenomenon in miRNAs expression and after that, we conduct an in-depth discussion about the regulation of DNA methylation regulators by epi-miRNAs in cancer cells.
DNA甲基化过程的紊乱可导致基因表达和功能的改变,最终引发恶性转化。研究表明,在癌症中,甲基化相关沉默使抑癌基因失活的效应与基因突变相当。DNA甲基化机制由多个基因构成,包括具有DNA甲基转移酶活性的基因、启动子区域结合甲基化胞嘧啶的蛋白质以及具有去甲基化酶活性的酶类。大量证据表明,DNA甲基化机制可受被称为表观miRNA(epi-miRNAs)的微小RNA调控。众多研究证实,DNA甲基化调节因子(如上epi-miRNAs)的失调在致癌过程中起关键作用;因此,通过恢复癌症中这种调控系统,可逆转细胞的恶性转化能力。可以预见的是,对癌细胞中这些epi-miRNAs的识别不仅能够揭示致癌过程中的新分子实体,还有望为癌症治疗提供新的靶点。本文首先概述癌症中甲基化改变及其对miRNAs表达的影响,随后深入探讨癌细胞中epi-miRNAs对DNA甲基化调节因子的调控作用。
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