The roles of epigenetic regulation in cholangiocarcinogenesis - 13/09/23

Doi : 10.1016/j.biopha.2023.115290

Baiyin Zhong ^a,^{^{1
These authors contributed equally to this article.}}, Qicheng Liao ^a,^{^{1
These authors contributed equally to this article.}}, Xin Wang ^a,^{^{1
These authors contributed equally to this article.}}, Xiaonong Wang ^a, Jianhong Zhang ^a,^b,^⁎
^a Department of Hepatobiliary Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China
^b Ganzhou Key Laboratory of Hepatocellular Carcinoma, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China

^⁎Corresponding author at: Department of Hepatobiliary Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China.Department of Hepatobiliary Surgery, First Affiliated Hospital of Gannan Medical UniversityGanzhou341000China

Abstract

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 potential targets for the therapeutic management of CCA, and epigenetic targets may become diagnostic biomarkers of CCA.

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Graphical Abstract

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Highlights

•	Epigenetic regulation plays a role in the cholangiocarcinogenesis.
•	Aberrant histone modification promotes CCA development.
•	Aberrant DNA methylation promotes CCA development.
•	Epigenetic modification becomes a potential target for CCA treatment.

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Keywords : Cholangiocarcinoma, Epigenetic, Acetylation, Deacetylation, DNA methylation, Noncoding RNAs