J. C. Lee1,2, J. T. Zhao1, L. Bach2, J. Ip1, J. Gundara1, A. Glover1, J. Serpell3, S. Sidhu1 1University Of Sydney,Kolling Institute Of Medical Research,Sydney, NSW, Australia 2Monash University,Melbourne, VIC, Australia 3The Alfred Hospital,Department Of Surgery,Melbourne, VIC, Australia
Introduction: The potential for circulating miR-146b and miR-222 in papillary thyroid cancer (PTC) patients to be used as circulating biomarkers has recently been reported. This study aimed to demonstrate the presence of miR-146b and miR-222 in PTC-derived exosomes, and to investigate the potential role of these exosomes in an in vitro model.
Methods: Exosomes were isolated from the condition medium of PTC cells. Western blot of CD9 surface marker was used to confirm the isolation of exosomes. The miRNA contents of PTC cells, conditioned medium and exosomes were compared. Benign thyroid and PTC cells were treated with PTC-derived exosomes, and the changes in their proliferation were measured by the MTT assay.
Results:The isolated exosomes were positive for the CD9 surface marker on Western blots. The concentration of miR-222 was similar in the exosomes and PTC cells, but lower in the conditioned medium. On the other hand, the concentration of miR-146b was highest in the cells and lowest in the conditioned medium, with concentrations within the exosomes somewhere in between. Treatment with PTC-derived exosomes resulted in reduced proliferation of both benign and malignant thyroid follicular cells.
Conclusion:The results demonstrated that miR-146b and miR-222 are both secreted by PTC cells, packaged in exosomes. These can be used as circulating biomarkers. It appears that PTC cells may release exosomes that mediate a reduction of proliferation in other cells. This in turn would confer a survival advantage for the PTC cells.