Abstract
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.
Highlights
This study aimed to investigate the exact regulatory mechanisms of exosomal miR-34c in mediating communication between cholangiocarcinoma cells and fibroblasts
It is classified into intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma (ECC) subtypes based on the anatomical location
Based on nanoparticle tracking analysis (NTA), isolated exosomes showed a modal size of 110 ± 1.5 nm (Additional file 2: Fig. 2a)
Summary
This study aimed to investigate the exact regulatory mechanisms of exosomal miR-34c in mediating communication between cholangiocarcinoma cells and fibroblasts. Cholangiocarcinoma (CCA) is a malignancy arising from the epithelial cells of the biliary tree, comprising 3% of all the gastrointestinal malignancies [1, 2]. It is classified into intrahepatic cholangiocarcinoma (iCCA) and extrahepatic cholangiocarcinoma (ECC) subtypes based on the anatomical location. CAFs, as an activated subpopulation of fibroblasts, are the most common risk factor for tumor progression and metastasis [15, 16]. Studies suggest that proinflammatory proteins secreted by CAFs promote an antitumor immune response or support tumor pathogenesis by regulating the inflammatory microenvironment [17, 18]. The mechanism underlying the activation of fibroblasts in cholangiocarcinoma remains unknown
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