Karimzadeh Mohammad Reza, Pourdavoud Peyman, Ehtesham Naeim, Qadbeigi Mohaddese, Asl Masood Movahedi, Alani Behrang, Mosallaei Meysam, Pakzad Bahram
Department of medical Genetics, School of Medicine, Bam University of Medical Sciences, Bam, Iran.
Iranian Red Crescent Society, Tehran, Iran.
Cancer Gene Ther. 2021 Apr;28(3-4):157-174. doi: 10.1038/s41417-020-00210-7. Epub 2020 Aug 10.
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甲基化过程的破坏会导致基因表达和功能的改变，最终导致恶性转化。通过这种方式，研究表明，在癌症中，甲基化相关的沉默使肿瘤抑制基因失活，其效果与突变一样。DNA甲基化机制由几个基因组成，包括具有DNA甲基转移酶活性的基因、与启动子区域甲基化胞嘧啶结合的蛋白质以及具有去甲基化酶活性的酶。基于大量证据，DNA甲基化机制可能受称为表观miRNA的微小RNA（miRNA）调控。许多研究表明，像上游表观miRNA这样的DNA甲基化调节因子的失调对于致癌作用是不可或缺的；因此，通过恢复癌症中的这种调节系统，可以逆转这些细胞的恶性能力。可以想象，识别癌细胞中的这些表观miRNA不仅可以揭示致癌过程中的新分子实体，还可以为癌症治疗提供有前景的靶点。在这篇综述中，首先，我们概述了癌症中的甲基化改变及其对miRNA表达的影响，然后，我们深入讨论了癌细胞中表观miRNA对DNA甲基化调节因子的调控。
