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Cancer Cell International
Published in: Cancer Cell International 1/2021

01-12-2021 | Cholangiocarcinoma | Primary research

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

Authors: Xinglei Qin, Min Lu, Gang Li, Yajun Zhou, Zhaoyang Liu

Published in: Cancer Cell International | Issue 1/2021

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Abstract

Background

This study aimed to investigate the exact regulatory mechanisms of exosomal miR-34c in mediating communication between cholangiocarcinoma cells and fibroblasts.

Methods

Exosomes 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.

Results

The 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.

Conclusions

Thus, miR-34c in exosomes was found to be a key player in regulating intercellular communication between tumor cells and fibroblasts.
Appendix
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Metadata
Title
Downregulation of tumor‐derived exosomal miR-34c induces cancer‐associated fibroblast activation to promote cholangiocarcinoma progress
Authors
Xinglei Qin
Min Lu
Gang Li
Yajun Zhou
Zhaoyang Liu
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2021
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01726-6

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