Benefiting from more precise imaging and radiotherapy, patients with locoregionally nasopharyngeal carcinoma (NPC) have a significantly higher survival rate. Nonetheless, distant metastasis is still the predominant mode of failure. Advances in cancer research have highlighted that pathological angiogenesis is necessary for tumor metastasis by offering oxygen, nutrients, or cell metastatic conduits. MicroRNAs (miRNAs), a class of small noncoding RNAs, are increasingly implicated in modulation of angiogenesis in physiological and pathological conditions. Currently, we detected that miR-23a was highly enriched in NPC tissues at the metastatic or premetastatic stage, and its levels in NPC were associated with microvessel density. Subsequently, we proved that alteration of miR-23a expression modulated the growth, migration, and tube formation of HUVECs in vitro and affected the blood vessel outgrowth in the zebrafish model. Considering the possibility that extracellular miR-23a was horizontally transferred from CNE2 cells to HUVECs, we analyzed miR-23a encapsulated in exosomes, showing that overexpression of exosomal miR-23a in NPC promoted angiogenesis both in vitro and in vivo. Moreover, we provided evidences that miR-23a regulated angiogenesis by directly targeting testis-specific gene antigen (TSGA10). Taken together, our findings revealed that metastasis-associated miR-23a from NPC-derived exosomes plays an important role in mediating angiogenesis by targeting TSGA10.
Nasopharyngeal cancer (NPC) is an endemic type of head and neck cancer with a high rate of cervical lymph node metastasis. Metastasis is the major cause of death in NPC patients. Increasing evidence indicates that exosomes play a pivotal role in promoting cancer metastasis by enhancing angiogenesis and ECM degradation. Matrix metalloproteinase 13 is an important kind of matrix proteinase that is often overexpressed in various tumors and increases the risk of metastasis. However, little is known about the potential role of MMP13‐containing exosomes in NPC. In this study, we found that MMP13 was overexpressed in NPC cells and exosomes purified from conditioned medium (CM) as well as NPC patients’ plasma. Transwell analysis revealed that MMP13‐containing exosomes facilitated the metastasis of NPC cells. Furthermore, siRNA inhibited the effect of MMP13‐containing exosomes on tumor cells metastasis as well as angiogenesis. The current findings provided novel insight into the vital role of MMP13‐containing exosomes in NPC progression which might offer unique insights for potential therapeutic strategies for NPC progressions.
Objective: The purpose of our study is to investigate the role of miR-17-5p in angiogenesis of nasopharyngeal carcinoma and the crosstalk between HUVECs and CNE-2 via exosomes.Methods: Firstly, flow cytometry, cell viability assay, transwell assay, and tube formation were used to explore the role of miR-17-5p in angiogenesis. Then zebrafish model was used to confirm effects of miR-17-5p on angiogenesis. qRT-PCR analysis and Immunofluorescence assay were used to explore the expression of miR-17-5p in NPC tissues and cells compared to the normal control. Besides, in vitro assays were used to analyze the biological functions of miR-17-5p in NPC. What's more, in vitro and in vivo assays were used to detect the function of exosomal miR-17-5p in angiogenesis. Finally, luciferase reporter assay and western bolt were used to determine the relationship between miR-17-5p and BAMBI.Results: We observed that high expression of miR-17-5p promoted angiogenesis in NPC. Also, high expression of miR-17-5p promoted the NPC cells proliferation and migration. To know whether there's any communication between HUVECs and NPC cells, exosomes derived from CNE-2 cells were collected. Further results showed that exosomal miR-17-5p secreted from NPC promoted the angiogenesis. What's more, in vitro assays revealed that miR-17-5p targets BAMBI and regulates AKT/VEGF-A signaling.Conclusions: Our study showed that exosomal miR-17-5p derived from NPC cells promotes angiogenesis via targeting BAMBI and regulates AKT/VEGF-A signaling.
The authors have withdrawn their manuscript whilst they perform additional experiments to test some of their conclusions further. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Abnormal angiogenesis and vascular permeability is important for the formation of nasal polyps (NPs). Increasing evidence has indicated that exosomes serve a vital role in modulating angiogenesis and vascular permeability. A disintegrin and metalloprotease 10 (ADAM10), an important type of proteinase that is overexpressed in various diseases, can influence angiogenesis and vascular permeability and has been observed in healthy nasal exosomes. To the best of our knowledge, the expression levels and the function of ADAM10 in NLF-derived exosomes from NPs has not been demonstrated previously. In order to determine the influence of exosomes derived from nasal lavage fluid (NLF) on angiogenesis and vascular permeability, 25 nasal polyp patients and 15 healthy volunteers were enrolled in the present study. NLF was collected from all of the subjects. Exosomes were isolated from NLF, visualized under transmission electron microscope and identified using western blot analysis. The effect of exosomes on human umbilical vein endothelial cells (HUVECs) was measured by tube formation and permeability assays in vitro. The expression of exosomal ADAM10 was also analyzed by western blotting. NLF-derived exosomes from NPs influenced proliferation, tube formation and the permeability of HUVECs. ADAM10 was highly expressed in NLF-derived exosomes from NPs when compared with healthy volunteers. Thus, NLF-derived exosomes from NPs promoted angiogenesis and vascular permeability, which may be associated with abundant ADAM10 in NP exosomes.
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