The roles of epigenetic regulation in cholangiocarcinogenesis

Cholangiocarcinoma (CCA), a heterogeneous malignancy of bile duct epithelial cells, is characterized by aggressiveness, difficult diagnosis, and poor prognosis due to limited understanding and lack of effective therapeutic strategies. Genetic and epigenetic alterations accumulated in CCA cells can cause the aberrant regulation of oncogenes and tumor suppressors. Epigenetic alterations with histone modification, DNA methylation, and noncoding RNA modulation are associated with the carcinogenesis of CCA. Mutation or silencing of genes by various mechanisms can be a frequent event during CCA development. Alterations in histone acetylation/ deacetylation at the posttranslational level, DNA methylation at promoters, and noncoding RNA regulation contribute to the heterogeneity of CCA and drive tumor development. In this review article, we mainly focus on the roles of epigenetic regulation in cholangiocarcinogenesis. Alterations in epigenetic modification can be po-tential targets for the therapeutic management of CCA, and epigenetic targets may become diagnostic biomarkers of CCA.

Automated summary

Cholangiocarcinoma (CCA) is a malignant tumor of bile duct epithelial cells with aggressiveness, difficult diagnosis, and poor prognosis. Genetic and epigenetic alterations, including histone modification, DNA methylation, and noncoding RNA modulation, play a role in the development of CCA. Alterations in epigenetic regulation can be potential therapeutic targets and diagnostic biomarkers for CCA.