Loginov V I, Rykov S V, Fridman M V, Braga E A
Institute of General Pathology and Pathophysiology, Moscow, 125315, Russia.
Biochemistry (Mosc). 2015 Feb;80(2):145-62. doi: 10.1134/S0006297915020029.
Interaction between microRNA (miRNA) and messenger RNA of target genes at the posttranscriptional level provides fine-tuned dynamic regulation of cell signaling pathways. Each miRNA can be involved in regulating hundreds of protein-coding genes, and, conversely, a number of different miRNAs usually target a structural gene. Epigenetic gene inactivation associated with methylation of promoter CpG-islands is common to both protein-coding genes and miRNA genes. Here, data on functions of miRNAs in development of tumor-cell phenotype are reviewed. Genomic organization of promoter CpG-islands of the miRNA genes located in inter- and intragenic areas is discussed. The literature and our own results on frequency of CpG-island methylation in miRNA genes from tumors are summarized, and data regarding a link between such modification and changed activity of miRNA genes and, consequently, protein-coding target genes are presented. Moreover, the impact of miRNA gene methylation on key oncogenetic processes as well as affected signaling pathways is discussed.
微小RNA（miRNA）与靶基因信使核糖核酸在转录后水平的相互作用为细胞信号通路提供了精确调控。每个miRNA可参与调控数百个蛋白质编码基因，反之，多个不同的miRNA通常靶向一个结构基因。与启动子CpG岛甲基化相关的表观遗传基因失活在蛋白质编码基因和miRNA基因中都很常见。本文综述了miRNA在肿瘤细胞表型形成中的功能数据。讨论了位于基因间和基因内区域的miRNA基因启动子CpG岛的基因组组织。总结了关于肿瘤中miRNA基因CpG岛甲基化频率的文献及我们自己的研究结果，并展示了有关这种修饰与miRNA基因以及蛋白质编码靶基因活性改变之间联系的数据。此外，还讨论了miRNA基因甲基化对关键致癌过程以及受影响信号通路的影响。
