2217 ISSN 1479-6694 Future Oncol. (2017) 13(25), 2217–2222 part of 10.2217/fon-2017-0363 © 2017 Future Medicine Ltd COMMENTARY Epigenetic regulation by DNA methylation and miRNA molecules in cancer Veronika Holubekova* ,1 , Andrea Mendelova 2 , Karin Jasek 1 , Sandra Mersakova 1 , Pavol Zubor 1,3 & Zora Lasabova 1,4 First draft submitted: 27 July 2017; Accepted for publication: 23 August 2017; Published online: 4 October 2017 1 Division of Oncology, Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, SK-03601 Martin, Slovakia 2 Division of Molecular Medicine, Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, SK-03601 Martin, Slovakia 3 Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, SK-03601 Martin, Slovakia 4 Department of Molecular Biology, Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, SK-03601 Martin, Slovakia *Author for correspondence: Tel.: +421 43 2633 651; veronika.holubekova@jfmed.uniba.sk KEYWORDS • circulating markers • DNA methylation • epigenetic silencing • miRNA The leading causes of death across the world are cancer, cardiovascular diseases and chronic lower respiratory diseases, cerebrovascular diseases, Alzheimer’s disease, diabetes and other [1] . All of these conditions still appear due to the immense scope of research and management at basic molecular or targeted clinical level. In normal eukaryotic organisms, the key process in embryonic development, differentiation, imprinting, chromosome stability and inactivation of large chromosomal domains – for example, X-chromosome is epigenetic silencing. One well-studied epigenetic modification is DNA methylation that represents a heritable state without altered nucleotide sequence; moreover, modified patterns in DNA methylation are predominantly found in many cancers [2] . This com- mentary covers actual information about epigenetic regulation of gene expression by DNA methyla- tion and miRNA molecules. Recent findings about DNA methylation may also have an influence on miRNA promoter region and may regulate miRNA expression in normal and cancer tissue. Recent studies focused on DNA methylation DNA methylation occurs as a covalent addition of a methyl group generally in cytosine within CpG dinucleotides that are concentrated in CpG islands (CGIs). CGIs are GC-rich, CpG-rich, mostly unmethylated when localized at transcription start sites of genes or predominantly methylated when scattered across the genome (within gene bodies – intragenic or between genes – intergenic). CpGs outside of transcription start sites are also sites of transcriptional initiation during development and become methylated hence lose these properties. Silencing of CGI promoters by methylation and demethylation reactions is differentially sensitive to the distance between interacting CpGs (CpG clustering) [3], and accomplished through dense CpG methylation or polycomb recruit- ment. CGIs are therefore equipped to influence local chromatin structure and simplify regulation of gene activity. CGIs have also been found in tissue-specific gene promoters and are known as tissue-specific differentially methylated regions (T-DMRs) [4] . Tissue-specific DNA methylation pattern is important for tissue-specific gene regulation, tissue-specific genes are not expressed in “DNA methylation pattern and miRNA expression profile allow characterization of tumor tissue origination and metastatic potential, and are suitable diagnostic and prognostic markers that might be observed in early stages of cancer. ”