If genetics studies the processes that lead to changes in our genes in DNA, then epigenetics examines the changes in gene activity in which the DNA structure remains the same, and the factors that affect this activity. He introduced the classical concept of developmental genetics - the "epigenetic landscape". According to the definition of K. Waddington, "epigenetic landscape" is branching pathways (channels) of possible directions that the cell passes through in the process of differentiation [4]. According to Zhao Z. et al. (2011), the directions of these channels, their terminal stage and the result of differentiation depend on the action of many external and internal factors that narrow the cell potency at each fork in the epigenetic landscape [5].
Micro-RNA (micro-RNA, miR) is a vivid representative of such internal epigenetic factors. These are small noncoding molecules, on average consisting of 20-22 nucleotides. They participate in almost all functions of the cell due to the ability to regulate the expression of genes at the posttranscriptional stage. Created in 2012, the world database miRBase micro-RNA (www.mirbase.org) contains a description of about 5000 micro-RNA, of which more than 2,000 are studied in human. And each of them regulates a set of target genes [Bartel, 2009] [6]. In medical scientific circles even the term "RNomic" appeared - the identification of all non-coding RNAs and their measurement in a given person under specific conditions. Each individual micro-RNA regulates a separate cascade of genes, activating the expression of some cascade genes and suppressing the expression of others. Some groups of micro-RNAs can participate in the regulation of several processes at the cellular level. For example, micro-RNA-21 is involved both in blocking apoptosis, angiogenesis, and in the development of fibrosis. On micro-RNA, modern oncology holds great hopes. It is believed that in the near future, RNomics will: • Conduct early diagnosis of diseases, • Differentiate benign tumors from malignant neoplasms by serum, • Determine the tumor histotype, stage of development, the potential for metastasis, • Influence the choice of therapy, • Monitor the effect of therapeutic effects (radiation and chemotherapy), • Predict survival. MicroRNAs can be encoded in any part of the genome. Most (61%) of the micro-RNA genes are located in the regions of introns of protein-coding genes. However, micro-RNA genes can be localized in the exons (35%) or intergenic regions (4%) [7, 8].
Micro-RNAs are transcribed from genes called miRNA genes, RNA polymerase II (polII), some by polIII. In this case, a primary microRNA is formed which is cleaved in the cell nucleus by Ribonuclease III Drosha with the formation of premcrRNA, and then in the cytoplasm, Ribonuclease III Dicer is transformed into mature double-stranded form of microRNA. One of the strands of mature micro-RNA becomes part of the ribonucleic complex RISC (RNA-induced silencing complex). The ends of the microRNA bind to the domains of the main catalytic protein of the complex Argonaute (Ago) and become inaccessible to the action of exonucleases, while the central part of the micro-RNA retains the ability to interact with the target [9]. It is generally believed that microRNAs perform predominantly negative post-translational regulation of gene expression by stopping the translation of matrix RNA (mRNA) and its subsequent degradation [10].
To date, there are three main mechanisms of gene regulation with the help of micro-RNAs [11]: - repression of translation, - direct degradation of mRNA, - micro-RNA-mediated destruction of mRNA. Helwak A. et al. based on an analysis of more than 18,000 microRNA-mRNA interactions, concluded that any region of matrix mRNA directly participating in the synthesis of proteins by a cell can become a target of RISC [12].
In this case, according to the authors' data, in 42% of cases, the interaction occurred with the coding sequence of mRNA, and in 23% and 4% - with non-coding regions 3'UTR and 5'UTR, respectively.