Braga E A, Khodyrev D S, Loginov V I, Pronina I V, Senchenko V N, Dmitriev A A, Kubatiev A A, Kushlinskii N E
Genetika. 2015 Jun;51(6):668-84.
The methylation of CpG islands in promoter regions, together with the interaction of miRNAs with the mRNAs of their target genes on the posttranscriptional level, are complex epigenetic mechanisms that perform the delicate and dynamic regulation of genes and signal transduction pathways in the cell. This review summarizes the results obtained by the authors, as well as the literature data, on the roles of methylation in regulating the protein-coding genes of chromosome 3 and a number of miRNA genes in clear-cell renal cell carcinomas. The results are based on the use of genomic NotI-microarrays (which allow the identification of both methylation and deletions in genes containing CpG islands) and on some other approaches. The application of NotI-microarray technology to the analysis of the chromosome-3 short arm, a region of frequent deletions in tumors, gave us the opportunity to identify many novel genes associated with kidney cancer pathogenesis. The relationship between alterations in the expression leyels and methylation of chromosome 3 genes, kidney cancer progression, and metastasis was shown. New microRNAs involved in kidney cancer pathogenesis were identified as well. The functions of microRNA genes methylated in kidney cancer were discussed.
启动子区域CpG岛的甲基化，以及微小RNA（miRNA）在转录后水平与其靶基因的信使核糖核酸（mRNA）之间的相互作用，是复杂的表观遗传机制，它们对细胞中的基因和信号转导通路进行精细而动态的调控。本综述总结了作者所获得的结果以及文献数据，内容涉及甲基化在调控透明细胞肾细胞癌中3号染色体的蛋白质编码基因和一些miRNA基因方面的作用。这些结果基于基因组NotI微阵列（可识别含CpG岛基因中的甲基化和缺失情况）以及其他一些方法。将NotI微阵列技术应用于肿瘤中常发生缺失的3号染色体短臂区域的分析，使我们有机会鉴定出许多与肾癌发病机制相关的新基因。研究显示了3号染色体基因的表达水平改变与甲基化、肾癌进展及转移之间的关系。同时也鉴定出了参与肾癌发病机制的新型微小RNA。还讨论了在肾癌中发生甲基化的微小RNA基因的功能。
