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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2020 | Metastasis | Research

Exosomal circRNA-100338 promotes hepatocellular carcinoma metastasis via enhancing invasiveness and angiogenesis

Authors: Xiu-Yan Huang, Zi-Li Huang, Jin Huang, Bin Xu, Xin-Yu Huang, Yong-Hua Xu, Jian Zhou, Zhao-You Tang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2020

Abstract

Background

Exosomes play crucial roles in regulating the crosstalk between normal and cancer cells in the tumor microenvironment, and in regulating cancer proliferation, migration and invasion through their cargo molecules.

Methods

We analyzed the pro-invasiveness of exosomal circRNA-100,338 in HCC using the transwell invasion assay. The co-culture of human umbilical vein endothelial cells (HUVEC) and exosomes derived from HCC cell lines were used to evaluate the impact of HCC derived exosomes on HUVEC. Nude mice models were used to validate the findings in vitro. Clinically, quantitative RT-PCR was used to quantify the expression of serum exosomal circRNA-100,338 in HCC patients at both pre-surgery within one week and post-surgery within three weeks.

Results

We aim to investigate the pro-invasive role of exosomal circRNA-100,338 in HCC metastasis. We for the first time demonstrated that circRNA-100,338 was highly expressed in both highly metastatic HCC cells and their secreted exosomes. The transwell invasion assay showed that the overexpression or knockdown of exosomal circRNA-100,338 significantly enhanced or reduced the invasive abilities of HCC cells. Subsequently, in vitro and in vivo assays showed that exosomal circRNA-100,338 affected the cell proliferation, angiogenesis, permeability, and vasculogenic mimicry (VM) formation ability of human umbilical vein endothelial cells (HUVEC), and tumor metastasis. Furthermore, we also observed that the persistent high expression of exosomal circRNA-100,338 in serum of HCC patients who underwent curative hepatectomy may be a risk indicator of pulmonary metastasis and poor survival.

Conclusions

Our findings indicated that metastatic ability of HCC cells could be enhanced by transferring exosomal circRNA-100,338 to recipient HUVECs, which could affect proangiogenic activity by regulating angiogenesis.

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Title: Exosomal circRNA-100338 promotes hepatocellular carcinoma metastasis via enhancing invasiveness and angiogenesis
Authors: Xiu-Yan Huang
Zi-Li Huang
Jin Huang
Bin Xu
Xin-Yu Huang
Yong-Hua Xu
Jian Zhou
Zhao-You Tang
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Metastasis
Hepatocellular Carcinoma
Hepatocellular Carcinoma
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2020
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-020-1529-9

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