Some Aspects of Carcinogenesis Associated with Genetic and Epigenetic Factors

详细

Abstract—Various authors have shown that the numerous instances of spontaneous DNA damage (DNA breaks, change in bases) that occur daily in a cell as a result of the metabolism of the human body are the basis of mutational selection. Mutant cells have certain advantages in the microenvironment, which changes due to age characteristics. This contributes to the formation of cancer clones and their dissemination. A significant role in this process belongs to hereditary factors; at the same time, there are a number of hereditary diseases (Xeroderma pigmentosum, etc.) that in most cases lead to the occurrence of cancer. Herein, we describe a number of associated genes that control cellular homeostasis and, at the same time, are suppressor genes; changes in their activity or mutations in their structure contribute to carcinogenesis. The role of epigenetic factors, including noncoding regulatory RNAs, the organization of the chromatin structure, and methylation in the carcinogenesis processes is considered. Modulation of the functional activity of genes is carried out by noncoding RNAs; each RNA can have several target genes and can, in turn, be affected by different genes. Regulatory RNAs include microRNAs and long noncoding RNA proteins, changes in the activity of which can serve as biomarkers of disease onset, have a predictive value, and can be used as a target for therapy. New data on the role of noncoding RNAs, methylation, and chromatin organization in carcinogenesis are presented. Our data on the use of the expression level of some genes and noncoding RNAs as prognostic indicators suitable for the evaluation of treatment efficacy for a number of tumors are presented. Special attention is paid to the structural organization of chromatin and methylation in carcinogenesis, as well as to the interaction of cellular structures that affect the activity of genes and their regulation in carcinogenesis. A brief assessment of the carcinogenic effect of exogenous factors such as natural (cosmic factors and some natural compounds) and anthropogenic ones (radiation, chemicals, and cancer viruses) is given.