Downregulation of tumor‐derived exosomal miR-34c induces cancer‐associated fibroblast activation to promote cholangiocarcinoma progress

Cancer Cell International

Min Lu¹  Xinglei Qin²  Gang Li²  Yajun Zhou²  Zhaoyang Liu² 

[1]Department of Cardiology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, 450003, Zhengzhou, Henan, China

[2]Department of Hepatobiliary Surgery, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, No.7 Weiwu Road, 450003, Zhengzhou, Henan, China

关键词: Cholangiocarcinoma;    Fibroblasts;    Exosomes;    miR-34c;    WNT1;   

DOI  :  10.1186/s12935-020-01726-6

来源: Springer

【 摘 要 】

BackgroundThis study aimed to investigate the exact regulatory mechanisms of exosomal miR-34c in mediating communication between cholangiocarcinoma cells and fibroblasts.MethodsExosomes were isolated from HuCCT-1 and HIBEC cells using differential ultracentrifugation and identified by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) method. Real-time quantitative PCR (qRT-PCR) and western blotting analyses were performed to assess the levels of pro-inflammatory factors, and fibroblast-related proteins and Wnt-linked signaling pathway proteins, respectively. Exosome-tracking was performed with confocal microscopy. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and Transwell assays were used to measure cell proliferation and migration, respectively. Further, the oncogenicity of cholangiocarcinoma cells was analyzed in nude mice transplanted tumor model.ResultsThe analysis suggested that the expression of miR-34c was decreased in exosomes from HuCCT-1 cells. Moreover, miR-34c in exosomes mediated fibroblast activation by directly targeting WNT1. Additionally, cancer-associated fibroblasts (CAFs) activated by downregulation of exosomal miR-34c promoted cholangiocarcinoma progression.ConclusionsThus, miR-34c in exosomes was found to be a key player in regulating intercellular communication between tumor cells and fibroblasts.

【 授权许可】

CC BY