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Tian, Xiaoyan; Liu, Yuehui; Wang, Zhi; Wu, Shuhong
Molecular therapy. Nucleic acids, 06/2021, Volume: 24Journal Article
The current study aimed to explore the role of tumor-derived extracellular vesicles (EVs) in angiogenesis during nasopharyngeal carcinoma (NPC). NPC biopsy specimens were initially collected. Human umbilical vein endothelial cells (HUVECs) were co-cultured with EVs isolated from NPC cells, after which their migration, invasion, as well as vessel-like tube formation were evaluated by Transwell chamber systems and Matrigel-based angiogenesis assays. The pro-angiogenic activities of EVs as well as the candidate microRNA (miRNA or miR) were examined using an in vivo Matrigel angiogenesis model. The results indicated that the levels of miR-144 in the NPC tissues were upregulated when compared to the nasopharyngeal normal tissues in addition to the identification of a positive correlation with the expression of CD31. Moreover, our data indicated that miR-144 was highly enriched in EVs from NPC cells and then ultimately enhanced the migration and invasion of HUVECs and vessel-like tubes in vitro and in vivo. Notably, miR-144 was identified as a mediator in NPC-EV-induced regulatory effects through the inhibition of the target gene FBXW7 and promotion of the transcriptional factor HIF-1α-dependent vascular endothelial growth factor (VEGF-A). Taken together, the key findings of the current study highlighted the role of miR-144 as an extracellular pro-angiogenic mediator in NPC tumorigenesis. Display omitted Our data elucidated that miR-144 delivered by nasopharyngeal-carcinoma-derived extracellular vesicles exerted pro-angiogenic effects on NPC tumorigenesis, which was achieved by the FBXW7/HIF-1α/VEGF-A axis, shedding light on EV-based therapies for NPC treatment.
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