DNA methylation of channel-related genes in cancers

• Epigenetic alterations of ionic channel-related genes may contribute to carcinogenesis via regulating their expression.
• Hypermethylation of ion channel gene promoter is frequent in cancer where it is associated with loss of their expression.
• Hypomethylation of ion channels is less frequent than hypermethylation, and is associated with increase of their expression.
• Ion channel methylation status is often associated with a poor prognosis, and may be potentially used as a prognostic factor.

DNA methylation at CpG sites is an epigenetic mechanism that regulates cellular gene expression. In cancer cells, aberrant methylation is correlated with the abnormalities in expression of genes that are known to be involved in the particular characteristics of cancer cells such as proliferation, apoptosis, migration or invasion. During the past 30 years, accumulating data have definitely convinced the scientific community that ion channels are involved in cancerogenesis and cancer properties. As they are situated at the cell surface, they might be prime targets in the development of new therapeutic strategies besides their potential use as prognostic factors. Despite the progress in our understanding of the remodeling of ion channels in cancer cells, the molecular mechanisms underlying their over- or down-expression remained enigmatic. In this review, we aimed to summarize the available data on gene promoter methylation of ion channels and to investigate their clinical significance as novel biomarkers in cancer. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.