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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2018

Open Access 01-12-2018 | Research

Circular RNA IARS (circ-IARS) secreted by pancreatic cancer cells and located within exosomes regulates endothelial monolayer permeability to promote tumor metastasis

Authors: Jie Li, Zhonghu Li, Peng Jiang, Minjie Peng, Xi Zhang, Kai Chen, Hui Liu, Huaqiang Bi, Xiangde Liu, Xiaowu Li

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

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Abstract

Background

Recent studies show that exosomes are involved in intercellular communication and that abundant circular RNAs (circRNAs) are present within exosomes. However, whether these exosomal circRNAs contribute to tumor invasion and metastasis remains unclear, as do their associated mechanisms.

Methods

Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to measure the expression levels of circ-IARS in 85 pancreatic ductal adenocarcinoma (PDAC) tissues, plasma exosomes, and Hs 766 T, Hs 766 T-L2 and human microvascular vein endothelial (HUVECs) cells. RhoA, ZO-1 and RhoA-GTP levels were detected by qRT-PCR and western blotting (WB); RhoA activity analysis was also performed. Transwell assays were performed to examine changes in endothelial monolayer permeability, and immunofluorescence and WB were employed to evaluate F-actin expression and focal adhesion. Finally, an animal experiment was performed to detect the contribution of circ-IARS to cancer metastasis.

Results

circ-IARS expression was up-regulated in pancreatic cancer tissues and in plasma exosomes of patients with metastatic disease. Circ-IARS was found to enter HUVECs through exosomes and promote tumor invasion and metastasis. Circ-IARS expression was positively correlated with liver metastasis, vascular invasion, and tumor-node-metastasis (TNM) stage and negatively correlated with postoperative survival time. Overexpression of circ-IARS significantly down-regulated miR-122 and ZO-1 levels, up-regulated RhoA and RhoA-GTP levels, increased F-actin expression and focal adhesion, enhanced endothelial monolayer permeability, and promoted tumor invasion and metastasis.

Conclusions

circ-IRAS accesses HUVECs via exosomes derived from pancreatic cancer cells followed by increased endothelial monolayer permeability. Furthermore, this process promotes tumor invasion and metastasis. The results of this study suggest that the presence of circRNAs in exosomes may be important indicator for early diagnosis and prognostic prediction in PDAC.
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Metadata
Title
Circular RNA IARS (circ-IARS) secreted by pancreatic cancer cells and located within exosomes regulates endothelial monolayer permeability to promote tumor metastasis
Authors
Jie Li
Zhonghu Li
Peng Jiang
Minjie Peng
Xi Zhang
Kai Chen
Hui Liu
Huaqiang Bi
Xiangde Liu
Xiaowu Li
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-018-0822-3

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