Department of Hepatobiliary Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China.
Department of Hepatobiliary Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China; Ganzhou Key Laboratory of Hepatocellular Carcinoma, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China.
Biomed Pharmacother. 2023 Oct;166:115290. doi: 10.1016/j.biopha.2023.115290. Epub 2023 Aug 7.
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.
胆管癌（CCA）是一种具有异质性的胆管上皮细胞恶性肿瘤，其侵袭性强、诊断困难、预后差，这主要是由于对其发病机制的认识有限和缺乏有效的治疗策略。CCA 细胞中积累的遗传和表观遗传改变可导致癌基因和肿瘤抑制基因的异常调节。组蛋白修饰、DNA 甲基化和非编码 RNA 调节的表观遗传改变与 CCA 的发生有关。在 CCA 发展过程中，通过各种机制导致基因突变或基因沉默是一种常见事件。在翻译后水平上的组蛋白乙酰化/去乙酰化、启动子 DNA 甲基化和非编码 RNA 调节的改变导致了 CCA 的异质性，并驱动肿瘤的发展。在这篇综述文章中，我们主要关注表观遗传调控在胆管癌发生中的作用。表观遗传修饰的改变可能是 CCA 治疗管理的潜在靶点，并且表观遗传靶点可能成为 CCA 的诊断生物标志物。
