2Research Center of Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, Russia; fax: +7 (499) 324-0702; E-mail: email@example.com
3Research Institute for Genetics and Selection of Industrial Microorganisms, 117545 Moscow, Russia; fax: +7 (495) 315-0501; E-mail: firstname.lastname@example.org
4Vavilov Institute of General Genetics, Russian Academy of Sciences, 117971 Moscow, Russia; fax: +7 (499) 135-6213; E-mail: email@example.com
* To whom correspondence should be addressed.
Received September 11, 2014; Revision received September 29, 2014
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.
KEY WORDS: miRNA, CpG-islands, methylation, target genes, epigenetic mechanisms, oncogenesis