Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210000, P. R. China.
Nanjing Medical University, Nanjing, Jiangsu, 210000, P. R. China.
Cancer Commun (Lond). 2020 Dec;40(12):655-680. doi: 10.1002/cac2.12109. Epub 2020 Nov 3.
Cholangiocarcinoma (CCA), a cancer with a relatively low incidence rate, is usually associated with poor prognosis. Current modalities for the diagnosis and treatment of CCA patients are still far from satisfactory. In recent years, numerous long noncoding RNAs (lncRNAs) have been identified as crucial players in the development of various cancers, including CCA. Abnormally expressed lncRNAs in CCA, regulated by some upstream molecules, significantly influence the biological behavior of tumor cells and are involved in tumor development through various mechanisms, including interactions with functional proteins, participation in competing for endogenous RNA (ceRNA) regulatory networks, activation of cancer-related signaling pathways and epigenetic modification of gene expression. Furthermore, several lncRNAs are closely associated with the clinicopathological features of CCA patients, and are promising biomarkers for diagnosing and prognostication of CCA. Some of these lncRNAs play an important role in chemotherapy drug resistance. In addition, lncRNAs have also been shown to be involved in the inflammation microenvironment of CCA and malignant outcome of CCA risk factors, such as cholestatic liver diseases. In view of the difficulty of diagnosing CCA, more attention should be paid to detectable lncRNAs in the serum or bile. This review summarizes the recent knowledge on lncRNAs in CCA and provides a new outlook on the molecular mechanisms of CCA development from the perspective of lncRNAs. Moreover, we also discussed the limitations of the current studies and differential expression of lncRNAs in different types of CCA.
胆管癌（CCA）是一种发病率相对较低的癌症，通常预后较差。目前用于诊断和治疗 CCA 患者的方法仍远远不能令人满意。近年来，大量的长链非编码 RNA（lncRNA）被鉴定为包括 CCA 在内的各种癌症发展的关键参与者。CCA 中异常表达的 lncRNA 受一些上游分子调控，通过多种机制显著影响肿瘤细胞的生物学行为，并通过与功能蛋白相互作用、参与竞争性内源 RNA（ceRNA）调控网络、激活癌症相关信号通路和基因表达的表观遗传修饰等方式参与肿瘤发生。此外，一些 lncRNA 与 CCA 患者的临床病理特征密切相关，是诊断和预测 CCA 的有前途的生物标志物。其中一些 lncRNA 在化疗药物耐药性中发挥重要作用。此外，lncRNA 还被证明参与 CCA 的炎症微环境和 CCA 危险因素的恶性结局，如胆汁淤积性肝病。鉴于 CCA 的诊断难度较大，应更加关注血清或胆汁中可检测到的 lncRNA。本综述总结了目前关于 lncRNA 在 CCA 中的研究进展，并从 lncRNA 的角度提供了对 CCA 发展的分子机制的新认识。此外，我们还讨论了目前研究的局限性和不同类型 CCA 中 lncRNA 的差异表达。
