CpG island hypermethylation, miRNAs, and human cancer

The importance of microRNAs (miRNAs) has rapidly increased in molecular biology in recent years due to their key role in several malignancies, including cancer. For this reason, it is crucial to unravel the physiological and disease-related mechanisms of regulation of these small, single-stranded RNAs. In cancer, aberrant DNA hypermethylation of tumor-suppressor genes, global genomic-DNA hypometh-ylation and disruption of histone-modification patterns are the main epigenetic alterations, and have consequently been widely studied. Some miRNAs are downregulated in cancer and act as bona fide tumor-suppressor genes, and this knowledge has led to the proposal of the hypothesis that miRNAs could be silenced by epigenetic mechanisms in transformed cells. It has recently been shown that miR-127 and miR-124a, two putative tumor-suppressor miRNAs, are methylated in tumor cells. Therefore, epigenomic tools can be effectively used in the search for new methylated tumor-suppressor miRNAs. From a clinical standpoint, this aberrant methylation can be reversed by epigenetic drugs, such as DNA demethylating agents and histone deacetylase inhibitors, restoring miRNA-expression levels and reverting the tumoral phenotype. Now that epigenetics and miRNAs have come together, the expectations are high.