Extravasation is a key step in tumor metastasis. EBV plays a crucial role in nasopharyngeal carcinoma metastasis. However, the functions and molecular mechanisms of EBV during tumor cell extravasation remains unclear. Here, we showed that the expression of pyroptosis-associated proteins is greater in the endothelial cells of metastatic NPC tissues than in those of nontumor tissues Exosomes derived from NPC cells promoted endothelial cell pyroptosis, vascular permeability, and tumor cell extravasation. The above results suggest that EBV is involved in NPC exosome-induced endothelial pyroptosis. To validate this hypothesis, we treated HUVECs with exosomes derived from three pairs of NPC cell lines. Exosomes derived from the CNE2-EBV, TW03-EBV and NPC43 Vector significantly promote endothelial cell pyroptosis compared to that in the control group. These results suggest that EBV may promote endothelial cell pyroptosis by directly packaging viral components or by virus-induced cellular components.
EBV produces non-coding RNAs, including a large family of BART miRNAs. To investigate the potential involvement of EBV BART miRNAs in this process, we induced the production of EBV virus using two lymphoma cell lines: Akata and B95-8. The above two kinds of viruses only share 10 common BART miRNAs. The viruses generated from the above two cell lines were used to infect HK1 cells. Subsequently, exosomes derived from infected HK-EBV cells were collected and used to treat HUVECs. There was no significant difference in endothelial cell pyroptosis between the two groups. This finding suggested that miRNAs shared by Akata- and B95-8- derived EBV might play a role in the regulation of endothelial cell pyroptosis. To investigate the miRNAs that regulate endothelial cell pyroptosis in exosomes, we sequenced serum exosomal miRNAs derived from EBV- healthy individuals, EBV+ healthy individuals, non-metastatic NPC patients and metastatic NPC patients. Moreover, we sequenced miRNAs in the exosomes of NP69 cells, NPC43 cells, C17 cells, and C666-1 cells. Compared to those in serum exosomes from the healthy individuals who were EBV- or EBV+, the levels of BART8-3p, BART2-5 and BART7-3p were significantly greater in serum exosomes from the patients with NPC, especially those with metastatic NPC. These miRNAs were also abundant in NPC cells Less...