Epigenetic alterations associated with cholangiocarcinoma (review).

Cholangiocarcinoma (CCA) is a highly lethal malignant tumor arising from the biliary tract epithelium. Chronic inflammatory conditions, including primary sclerosing cholangitis, liver fluke infestation, and hepatolithiasis, are considered risk factors, but the cause is still unknown in most cases. Recent advances in molecular pathogenesis have highlighted the importance of epigenetic alterations, including promoter hypermethylation and histone deacetylation, in the process of cholangiocarcinogenesis. More recently, research interest has been focusing on microRNA (mir), a major subtype of non-coding RNA. Mir is highly conserved among species and regulates the expression of specific target genes by binding to the 3'-untranslated regions of messenger RNA. The number of studies on a possible link between mir and various cancers is growing. This review provides a comprehensive overview of the genes currently known to be hypermethylated in CCA and their putative roles in cholangiocarcinogenesis. The epigenetic role of mir in the pathogenesis of CCA is also discussed.