Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 21, Issue 5, Pages 838-847Publisher
WILEY
DOI: 10.1111/jcmm.12941
Keywords
colorectal cancer; exosome; biomarker; GPC1; miRNA
Categories
Funding
- National 863 Hi-tech Project of China [2007AA021803, 2007AA021901, 2007AA021809, 2007AA021811]
- National Natural Science Foundation of China [81272972, 81472355]
- National Basic Research Program of China [2010CB833605]
- Hunan Provincial Nature Science Foundation [16JJ3056]
- Hunan Provincial Science Department Program [2014FJ6006]
- Incubation Program for National Natural Science Funds for Distinguished Young Scholar of Central South University [2010QYZD006]
- Open-End Fund for the Valuable and Precision Instruments of Central South University [CSUZC201638, CSUZC201634]
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Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. However, a biomarker for a sensitive and simple diagnostic test and highly effective target therapy of CRC is still clinically unavailable. This study is to investigate the evidence and significance of plasma GPC1 positive exosomes as a biomarker of CRC. Results showed that GPC1(+) exosomes were successfully isolated from tissues and plasma. The percentage of GPC1(+) exosomes and the GPC1 protein expression in exosomes from tumour tissues and plasma of CRC patients before surgical treatment was significantly elevated compared to that in the peritumoural tissues and the plasma of healthy controls. miR-96-5p and miR-149 expression in tumour tissues and plasma of CRC patients as well as in the GPC1(+) exosomes from CRC patients were significantly decreased compared to that in the peritumoural tissues and the plasma of healthy controls. Two months after surgical treatment, levels of all tested markers significantly normalized. Overexpression of miR-96-5p and miR-149 significantly decreased GPC1 expression in HT-29 and HCT-116 cells, xenograft tumours, plasma in mice bearing HT-29 and HCT-116 tumours, and the secretion of GPC1(+) exosomes from the HT-29 and HCT-116 cells and xenograft tumours. Overexpression of miR-96-5p and miR-149 significantly decreased cell viability and increased cell apoptosis in HT-29 and HCT-116 cells, and inhibited the growth of xenograft HT-29 and HCT-116 tumours. In conclusion, the increased plasma GPC1(+) exosomes and reduced plasma miR-96-5p and miR-149 expression are specific markers for the diagnosis of CRC and targets for the therapy of CRC.
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