Another subset of miRNA families upregulated in alcoholics, including miR-1, miR-34, miR-152, miR-196, and miR-203, is regulated by epigenetic mechanisms (Sato et al., 2011), which could partly explain how environmental factors could be contributing to disease development. The respective transcriptional units for miR-34b/c and miR-203 both contain CpG islands, and the methylation levels of these CpG islands are inversely correlated with the expression level of the mature miRNA in various cancers, including CNS tumors (Kozaki et al., 2008; Furuta et al., 2010). miR-152 and miR-196a are also silenced by hypermethylation of CpG islands on the respective DNA loci (Hoffman et al., 2009; Tsuruta et al., 2011). It is interesting to note that several of the miRNAs that target factors involved in epigenetic remodeling could be conversely regulated by epigenetic mechanisms, suggesting that miRNAs are elements of epigenetic feedback regulatory loops that fine-tune activity of the pathway.
