Exosomes Carrying MicroRNA-155 Target Forkhead Box O3 of Endothelial Cells and Promote Angiogenesis in Gastric Cancer.
Exosomes Carrying MicroRNA-155 Target Forkhead Box O3 of Endothelial Cells and Promote Angiogenesis in Gastric Cancer.
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携带MicroRNA-155的外泌体靶向内皮细胞的叉头盒O3并促进胃癌血管生成
DOI：
10.1016/j.omto.2019.10.006
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Ba Yi
中科院分区：
文献类型：
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作者：
Zhou Zhengyang;Zhang Haiyang;Deng Ting;Ning Tao;Liu Rui;Liu Dongying;Bai Ming;Ying Guoguang;Ba Yi
胃癌由于其恶性增殖和转移而预后不良。这种困境的原因之一是GC强大的血管生成能力。考虑到肿瘤外泌体在肿瘤微环境中作为载体和通讯者的重要作用，我们探讨了外泌体微小RNA（miRNA）在调节血管生成中的作用。采用Western blotting和实时荧光定量PCR检测miRNA靶基因的蛋白和mRNA水平。为了检测细胞生物学功能的变化，我们预处理人脐静脉内皮细胞（HUVECs），分别与GC衍生的exosomes共培养，并直接转染不同的miRNA。此外，我们使用小鼠异种移植模型来验证miR-155对体内GC组织血管生成的影响。我们的研究证实，胃癌exosomes包裹的miR-155作为促血管生成的驱动因子，可以通过抑制FOXO 3a蛋白的表达，促进胃癌新生血管的生成，从而促进胃癌的进展。因此，miR-155有可能成为检测胃癌细胞迁移和血管生成的潜在生物标志物，并成为抗血管生成治疗的新靶点。
Gastric cancer (GC) has a poor prognosis due to its relentless proliferation and metastasis. One of the reasons for this plight is the formidable angiogenesis ability of GC. Considering the important role of cancer exosomes as carriers and communicators in the tumor microenvironment, we explored the role of exosome-microRNA (miRNA) in regulating angiogenesis. Western blotting and quantitative real-time PCR were used to measure the protein and mRNA levels of the miRNA target gene. To detect changes in cellular biological functions, we pretreated human umbilical vein endothelial cells (HUVECs) that were severally cocultured with GC-derived exosomes and transfected them with different miRNAs directly. Also, we used the mouse xenograft model to verify the effect of miR-155 on angiogenesis of GC tissues in vivo. Our study confirmed that miR-155, as a driver of angiogenesis, encapsulated by exosomes from GC can enhance the generation of new vessels for GC in vitro through inhibiting the expression of Forkhead box O3 (FOXO3a) protein, which led to the progression of GC. Therefore, miR-155 is probable to become a potential biomarker for the detection of migration and angiogenesis of GC, and serves as a novel target for anti-angiogenesis therapy.