A Circular RNA, Cholangiocarcinoma‐Associated Circular RNA 1, Contributes to Cholangiocarcinoma Progression, Induces Angiogenesis, and Disrupts Vascular Endothelial Barriers

• DOI: 10.1002/hep.31493
• Publication Date: 2020-08-04T20:50:33Z
• Authors: Yi Xu; Kaiming Leng; Yue Yao; Pengcheng Kang; Guanqun Liao; Yi Han; Guangjun Shi; Daolin Ji; Peng Huang; Wangyang Zheng; Zhenglong Li; Jinglin Li; Lining Huang; Liang Yu; Yongxu Zhou; Xingming Jiang; Hao Wang; Chunlong Li; Zhilei Su; Sheng Tai; Xiangyu Zhong; Zhidong Wang; Yunfu Cui
• Keywords: Circular RNA

Circular RNAs (circRNAs) and extracellular vesicles (EVs) are involved in various malignancies. We aimed to clarify the functions mechanisms of dysregulated circRNAs cells EVs cholangiocarcinoma (CCA).CircRNA microarray was used identify circRNA expression profiles CCA tissues bile-derived (BEVs). CCA-associated 1 (circ-CCAC1) measured by quantitative real-time PCR. The clinical importance circ-CCAC1 analyzed receiver operating characteristic curves, Fisher's exact test, Kaplan-Meier plots, Cox regression model. exosomal were explored human umbilical vein endothelial (HUVECs), respectively. Different animal models verify vitro results. RNA sequencing, bioinformatics, immunoprecipitation, pulldown, chromatin immunoprecipitation followed luciferase reporter assays determine regulatory networks HUVECs. Circ-CCAC1 levels increased cancerous bile-resident tissues. diagnostic prognostic values identified patients with CCA. For cells, cell progression sponging miR-514a-5p up-regulate Yin Yang (YY1). Meanwhile, YY1 directly bound promoter calcium modulating ligand activate its transcription. Moreover, from CCA-derived transferred monolayer disrupting barrier integrity inducing angiogenesis. Mechanistically, leakiness sequestering enhancer zeste homolog 2 cytoplasm, thus elevating SH3 domain-containing GRB2-like protein reduce intercellular junction proteins. In vivo studies further showed that circulating accelerated both tumorigenesis metastasis.Circ-CCAC1 plays a vital role metastasis may be an important biomarker/therapeutic target for