DNA Methylation, Its Mediators and Genome Integrity

Abstract

DNA methylation regulates many cellular processes, including embryonic development, transcription, chromatin structure, X-chromosome inactivation, genomic imprinting and chromosome stability. DNA methyltransferases establish and maintain the presence of 5-methylcytosine (5mC), and ten-eleven translocation cytosine dioxygenases (TETs) oxidise 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), which can be removed by base excision repair (BER) proteins. Multiple forms of DNA methylation are recognised by methyl-CpG binding proteins (MeCPs), which play vital roles in chromatin-based transcriptional regulation, DNA repair and replication. Accordingly, defects in DNA methylation and its mediators may cause silencing of tumour suppressor genes and misregulation of multiple cell cycles, DNA repair and chromosome stability genes, and hence contribute to genome instability in various human diseases, including cancer. Thus, understanding functional genetic mutations and aberrant expression of these DNA methylation mediators is critical to deciphering the crosstalk between concurrent genetic and epigenetic alterations in specific cancer types and to the development of new therapeutic strategies.

Promoter hypermethylation of the RECK gene is associated with its low expression and poor survival of esophageal squamous cell carcinoma

“…Furthermore, the results of a previous study supported the notion that RECK dsRNA formation in the promoter region has the potential to upregulate RECK gene expression (17). Gene promoter hypermethyla tion has been associated with the silencing of tumor-related genes, which is considered the most important epigenetic dis ruption in numerous tumors (18,19). In a previous study, hypermethylation of the RECK gene was partially reversed by epigallocatechin gallate treatment, and the mRNA expression level of RECK was significantly enhanced in oral squamous cell carcinoma cell lines (20).…”

Ageing as an Important Risk Factor for Cancer

“…These are important for the transition from embryonic to fetal stage (37), from youth to old age, from normal tissue to cancerous tissue (38). From this point of view, DNA methylation may be important link between ageing, genome instability and cancerogenesis (39). The role of epigenetics in inactivation of gene repair can be well demonstrated in gastrointestinal tumors, as well as in the case of triple-negative breast cancer.…”

Epigenetic regulation by DNA methylation and miRNA molecules in cancer

“…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 commentary covers actual information about epigenetic regulation of gene expression by DNA methylation and miRNA molecules.…”