TUMOR-DERIVED EXOSOMES PROMOTE TUMOR GROWTH,INVASION AND INHIBIT APOPTOSIS IN GASTRIC CANCER BY TRANSFERRING MIRNA-452
Jia jia Yang*, Meihong Chen, Guoxin Zhang
Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
BACKGROUND: Exosomes, a type of novel signaling molecules, are widely found in many body fluids. We found that the exosomes in plasma of gastric cancer patients was significantly higher than that of non-cancerous individuals, and the expression of Exo-miR-452 was significantly higher than that of non-cancerous patients. It suggests that it may be closely related to the occurrence and development of gastric cancer.
METHODS: The morphology of exosomes was directly observed by transmission electron microscopy. The size of exosomes was determined by Nanosight Analysis. The protein markers(CD9,CD63 and TSG-101) of exosomes were detected by Western blot. Real-time quantitative PCR was used to screen differentially expressed miRNAs in gastric cancer and non-cancerous patients. Detect the expression of protein by Western blot. Luciferase reporter gene was used to detect the binding sites of miRNA and target protein. Scanning electrons and confocal microscopy were used to track exosomes and observe their uptake by recipient cells.
RESULTS: We confirmed that the number of exosomes in the serum of patients with gastric cancer was higher than that of normal individuals, which was mainly secreted by gastric cancer cells.The expression of miR-452 contained in exosomes was also higher than that of normal individuals.The GC cell line SGC-7901 and BGC-823 were cultured in exosome-deleted medium, the growth and invasion of the cancer cells are decreased and the apoptosis are increased compared with untreated culture medium. Down-regulated the expression of miR-452 in exosomes by transfection can achieve the same effect.It is suggested that miR-452 may be transmitted by exosomes to promote the development of gastric cancer.
CONCLUSIONS: Our results suggest that exosomes may provide miR-452 to promote the growth,invasion and inhibit the apoptosis of gastric cancer, and serum exosome miR-452 can be used as a potential marker for the diagnosis and prognosis of gastric cancer, providing new ideas for the treatment of gastric cancer
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