Research progress of DNA methylation in colorectal cancer (Review)

Abstract

DNA methylation is one of the earliest and most significant epigenetic mechanisms discovered. DNA methylation refers, in general, to the addition of a methyl group to a specific base in the DNA sequence under the catalysis of DNA methyltransferase, with S‑adenosine methionine as the methyl donor, via covalent bonding and chemical modifications. DNA methylation is an important factor in inducing cancer. There are different types of DNA methylation, and methylation at different sites plays different roles. It is well known that the progression of colorectal cancer (CRC) is affected by the methylation of key genes. The present review did not only discuss the potential relationship between DNA methylation and CRC but also discussed how DNA methylation affects the development of CRC by affecting key genes. Furthermore, the clinical significance of DNA methylation in CRC was highlighted, including that of the therapeutic targets and biomarkers of methylation; and the importance of DNA methylation inhibitors was discussed as a novel strategy for treatment of CRC. The present review did not only focus upon the latest research findings, but earlier reviews were also cited as references to older literature.

Keywords: CRC; DNA methylation; biomarker; therapeutic target.

Figure 1.

Research progress of DNA methylation in CRC from six aspects. The present review discussed the mechanism, clinical practice and future prospects. CRC, colorectal cancer; CIN, chromosome instability; MSI, microsatellite instability.

Figure 2.

DNA methylation means that under the action of DNMT, S-adenosylmethionine adds methyl groups to the bases of DNA molecules. For example, sodium bisulfite can convert unmethylated cytosine into uracil, but cannot change the cytosine in methylated CpG (30). KRAS is the most important carcinogenic mutation in CRC. In CRC cells expressing activated KRAS, these KRAS need SLC25A22 to participate and be rapidly incorporated into the TAC. At the same time, SLC25A22 promotes the accumulation of succinic acid, resulting in increased DNA methylation. In CRC cells without KRAS mutation or KRAS mutation and SLC25A22 knockout, the expressed pre-adhesin gene was not methylated at these sites. DNMT, DNA methyltransferase; CRC, colorectal cancer; SLC25A22, solute carrier family 25 member 22; TAC, tricarboxylic acid cycle; Glu, glutamine.