Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China.
Department of Postanesthesia Care Unit & Surgical Anesthesia Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.
Cancer Lett. 2023 Jan 28;553:215980. doi: 10.1016/j.canlet.2022.215980. Epub 2022 Nov 4.
Cholangiocarcinoma (CCA) is the most common primary biliary malignancy with an adverse prognosis. Although its incidence is relatively low, early diagnosis is difficult due to the lack of specific symptoms. Current treatment options for CCA are limited, resulting in a low curative rate. Circular RNAs (circRNAs) have become a new research hotspot in recent years, and they are frequently dysregulated in CCA and may become therapeutic targets and prognostic biomarkers of CCA. Accumulating evidence has demonstrated that numerous dysregulated circRNAs are vital players in the etiopathogenesis of CCA. Aberrant expression of specific circRNAs was correlated with unfavourable clinical characteristics in CCA. Many studies have found that circRNAs are involved in the progression and development of CCA through various mechanisms, including competitive inhibition of miRNAs via the competing endogenous RNA (ceRNA) network, interaction with RNA-binding proteins (RBPs), activation of cancer-related signalling pathways, and regulation of proteins and peptides. Additionally, some circRNAs are involved in the inflammatory microenvironment of CCA and play a crucial role in chemotherapy drug resistance. Thus, they are essential for the early diagnosis and prediction of CCA, and more attention should be given to the roles and mechanisms of circRNAs in CCA. In this review, we summarize the abnormal expression of circRNAs in CCA and the specific inflammatory microenvironment involved, as well as the roles and mechanisms of circRNAs in the occurrence and development of CCA. We also review the latest knowle dge on circRNAs in CCA and discuss the challenges associated with the introduction of circRNAs into clinical practice and their potential clinical value.
胆管癌(CCA)是最常见的原发性胆道恶性肿瘤,预后不良。尽管其发病率相对较低,但由于缺乏特异性症状,早期诊断较为困难。目前 CCA 的治疗选择有限,导致治愈率较低。近年来,环状 RNA(circRNA)已成为新的研究热点,它们在 CCA 中经常失调,可能成为 CCA 的治疗靶点和预后生物标志物。越来越多的证据表明,许多失调的 circRNA 是 CCA 发病机制中的重要参与者。特定 circRNA 的异常表达与 CCA 的不良临床特征相关。许多研究发现,circRNA 通过多种机制参与 CCA 的进展和发展,包括通过竞争性内源性 RNA(ceRNA)网络竞争性抑制 miRNAs、与 RNA 结合蛋白(RBPs)相互作用、激活癌症相关信号通路以及调节蛋白质和肽。此外,一些 circRNA 参与 CCA 的炎症微环境,并在化疗药物耐药性中发挥关键作用。因此,它们对 CCA 的早期诊断和预测至关重要,应更加关注 circRNA 在 CCA 中的作用和机制。在这篇综述中,我们总结了 circRNA 在 CCA 中的异常表达及其涉及的特定炎症微环境,以及 circRNA 在 CCA 发生和发展中的作用和机制。我们还回顾了 CCA 中 circRNA 的最新知识,并讨论了将 circRNA 引入临床实践所面临的挑战及其潜在的临床价值。