Exosomal miR-17-5p promotes angiogenesis in nasopharyngeal carcinoma via targeting BAMBI

Exosomal miR-17-5p promotes angiogenesis in nasopharyngeal carcinoma via targeting BAMBI
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外泌体miR-17-5p通过靶向BAMBI促进鼻咽癌血管生成

DOI:
10.7150/jca.30757
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发表时间:
2019-01-01
期刊:
影响因子:
3.9
通讯作者:
You, Yiwen
You, Yiwen
中科院分区:
医学3区
文献类型:
--
作者:
Duan, Bingyue;Shi, Si;You, Yiwen

文献摘要

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目的:本研究旨在探讨miR-17-5p在鼻咽癌血管生成中的作用以及HUVECs与CNE-2通过外泌体的串扰。方法:首先通过流式细胞术、细胞活力测定、transwell实验、成管等方法探讨miR-17-5p在血管生成中的作用。然后利用斑马鱼模型证实miR-17-5p对血管生成的影响。采用qRT-PCR和免疫荧光法检测miR-17-5p在鼻咽癌组织和细胞中与正常对照的表达情况。此外,通过体外实验分析miR-17-5p在鼻咽癌中的生物学功能。此外,通过体外和体内检测外泌体miR-17-5p在血管生成中的功能。最后,采用荧光素酶报告基因法和western bolt检测miR-17-5p与BAMBI之间的关系。结果:我们观察到miR-17-5p的高表达促进了鼻咽癌血管生成。此外,miR-17-5p的高表达促进了鼻咽癌细胞的增殖和迁移。为了了解HUVECs和鼻咽癌细胞之间是否存在通信,收集了来自CNE-2细胞的外泌体。进一步结果表明,NPC外泌体分泌的miR-17-5p促进了血管生成。此外,体外实验显示miR-17-5p靶向BAMBI并调节AKT/VEGF-A信号通路。结论:我们的研究表明,来自鼻咽癌细胞的外泌体miR-17-5p通过靶向BAMBI促进血管生成,并调节AKT/VEGF-A信号。
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.