Oncotarget

Research Papers:

The clinical significance of circulating GPC1 positive exosomes and its regulative miRNAs in colon cancer patients

Jian Li, Bo Li, Caiping Ren _, Yuxiang Chen, Xiong Guo, Lin Zhou, Zha Peng, Yaping Tang, Yang Chen, Weidong Liu, Bin Zhu, Lei Wang, Xuxu Liu, Xiao Shi and Zixuan Peng

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Oncotarget. 2017; 8:101189-101202. https://doi.org/10.18632/oncotarget.20516

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Abstract

Jian Li1, Bo Li2, Caiping Ren3, Yuxiang Chen4, Xiong Guo1, Lin Zhou1, Zha Peng1, Yaping Tang1, Yang Chen1, Weidong Liu3, Bin Zhu3, Lei Wang3, Xuxu Liu3, Xiao Shi3 and Zixuan Peng3

1Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China

2Department of Pathology, Xiangya Medical School, Central South University, Changsha, Hunan 410078, China

3Cancer Research Institute, Xiangya Hospital, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China

4School of Pharmaceutical Science, Central South University, Changsha, Hunan 410013, China

Correspondence to:

Caiping Ren, email: rencaiping@csu.edu.cn

Yuxiang Chen, email: Chenyx08@yahoo.com

Keywords: colorectal cancer; exosome; biomarker; GPC1; miRNA

Received: May 31, 2017    Accepted: August 06, 2017    Published: August 24, 2017

ABSTRACT

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Recent study found an increased level of glypican-1 positive (GPC1+) plasma exosomes in patients with stage II CRC, but decreased levels of plasma miR-96-5p and miR-149. This study further investigated the clinical significance of plasma GPC1+ exosomes and plasma miR-96-5p and miR-149 levels in stage III CRC patients. To study the effect of these microRNAs on GPC1+ plasma exosomes, we isolated and purified exosomes and overexpressed human GPC1 and the microRNAs miR-96-5p and miR-149 by adenovirus vectors. Overexpression of GPC1 activated epithelial-mesenchymal transition (EMT) which then increased invasion and migration in HT29 and HCT-116 colon cancer cells. In contrast, silencing GPC1 expression and overexpressing miR-96-5p and miR-149 significantly inactivated EMT and decreased invasion and migration of HT29 and HCT-116 cells. miR-96-5p and miR-149 inhibitors significantly increased invasion and migration of HT29 and HCT-116 cells. Our results indicate that high levels of circulating GPC1 positive exosomes before and after surgery as well as low circulating miR-96-5p and miR-149 before surgery indicated a severe clinical status and poor prognosis in stage III colon cancer patients. We conclude that GPC1 can be a biomarker for relapse of stage III CRC and may be involved in EMT activation, invasion, and migration of colorectal cancer cells.


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