Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 333, Taiwan.
Department of Surgery and Liver Research Center, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 333, Taiwan.
Biomolecules. 2020 Sep 30;10(10):1396. doi: 10.3390/biom10101396.
Cholangiocarcinoma (CCA) is the most common biliary malignancy, and has a poor prognosis. The median overall survival with the standard-of-care chemotherapy (Gemcitabine and cisplatin) in patients with advanced-stage CCA is less than one year. The limited efficacy of chemotherapy or targeted therapy remains a major obstacle to improving survival. The mechanisms involved in drug resistance are complex. Research efforts focusing on the distinct molecular mechanisms underlying drug resistance should prompt the development of treatment strategies that overcome chemoresistance or targeted drug resistance. MicroRNAs (miRNAs) are a class of evolutionarily conserved, short noncoding RNAs regulating gene expression at the post-transcriptional level. Dysregulated miRNAs have been shown to participate in almost all CCA hallmarks, including cell proliferation, migration and invasion, apoptosis, and the epithelial-to-mesenchymal transition. Emerging evidence demonstrates that miRNAs play a role in regulating responses to chemotherapy and targeted therapy. Herein, we present an overview of the current knowledge on the miRNA-mediated regulatory mechanisms underlying drug resistance among CCA. We also discuss the application of miRNA-based therapeutics to CCA, providing the basis for innovative treatment approaches.
胆管癌（CCA）是最常见的胆道恶性肿瘤，预后不良。接受标准治疗化疗（吉西他滨和顺铂）的晚期 CCA 患者的中位总生存期不到一年。化疗或靶向治疗的疗效有限仍然是提高生存率的主要障碍。耐药机制复杂。专注于耐药性背后的不同分子机制的研究努力应该促使开发克服化疗耐药性或靶向药物耐药性的治疗策略。microRNAs（miRNAs）是一类进化上保守的短非编码 RNA，在转录后水平调节基因表达。失调的 miRNAs 已被证明参与几乎所有 CCA 的特征，包括细胞增殖、迁移和侵袭、细胞凋亡以及上皮-间充质转化。新出现的证据表明，miRNAs 在调节对化疗和靶向治疗的反应中发挥作用。本文综述了 miRNA 介导的耐药性调节机制在 CCA 中的研究现状。我们还讨论了 miRNA 治疗在 CCA 中的应用，为创新治疗方法提供了依据。
