越来越多的证据表明 miRNA 调节参与肿瘤发生和恶性表型的关键基因的表达。本项目旨在探讨miR-182-5p在胆管癌进展中的作用及机制。通过分析TCGA和GEO数据库，结合组织表达水平，确定miR-182-5p是其中之一。最有价值的研究 miRNA。 miR-182-5p 与下游靶基因之间的功能和关系均通过体外和体内实验验证。采用甲基化特异性PCR和亚硫酸氢盐测序检测下游基因启动子甲基化水平变化。我们发现miR-182-5p可以被胆管癌分泌的外泌体摄取。此外，外泌体衍生的miR-182-5p通过靶向ADK/SEMA5a促进血管内皮细胞增殖和迁移并诱导血管生成。随后，PI3K/AKT/mTOR 信号通路被激活，最终引起对吉西他滨和顺铂的耐药。我们的研究结果表明 miR-182-5p/ADK/SEMA5a 轴可能作为胆管癌的潜在治疗靶点。© 2023 John Wiley

Increasing evidence suggested that miRNAs regulated the expression of pivotal genes involved in oncogenesis and malignant phenotype. In this project, the purpose was to make an inquiry to the effect and mechanism of miR-182-5p in the progression of cholangiocarcinoma.By analysing TCGA and GEO databases, combined with tissue expression levels, miR-182-5p was identified as one of the most valuable miRNAs for research. The function and relationships between miR-182-5p and downstream target genes were both verified by in vitro and in vivo experiments. Methylation-specific PCR and bisulphite sequencing were used to detect the methylation level changes of downstream gene promoter.We found that miR-182-5p could be taken up by exosomes secreted from cholangiocarcinoma. Moreover, exosomal derived miR-182-5p promoted vascular endothelial cell proliferation and migration and induced angiogenesis by targeting ADK/SEMA5a. Subsequently, the PI3K/AKT/mTOR signalling pathway was activated and ultimately caused resistance to gemcitabine and cisplatin.Our findings suggested that the miR-182-5p/ADK/SEMA5a axis might serve as a potential therapeutic target for cholangiocarcinoma.© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.