miR-135b Delivered by Gastric Tumor Exosomes Inhibits FOXO1 Expression in Endothelial Cells and Promotes Angiogenesis (Retracted article. See vol. 30, pg. 2636, 2022)
miR-135b Delivered by Gastric Tumor Exosomes Inhibits FOXO1 Expression in Endothelial Cells and Promotes Angiogenesis (Retracted article. See vol. 30, pg. 2636, 2022)
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胃肿瘤外泌体递送的 miR-135b 抑制内皮细胞中 FOXO1 的表达并促进血管生成
DOI：
10.1016/j.ymthe.2019.06.018
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发表时间：
2019-10-02
影响因子：
12.4
通讯作者：
Ba, Yi
中科院分区：
文献类型：
--
作者：
Bai, Ming;Li, Jialu;Ba, Yi
作为细胞间通讯介质的外泌体是含有蛋白质、脂质、mRNA和microRNA（miRNA）的纳米级膜囊泡。此外，外泌体在肿瘤的发展中起着重要作用。胃癌血管生成旺盛是其恶性生长的原因之一。药物和其他治疗方法并不能很好地解决GC中的血管生成问题。在这里，我们发现外泌体递送的miRNA极大地促进了GC中的血管生成。胃癌组织中FOXO 1表达下调。在测量过表达microRNA-135 b（miR-135 b）的慢病毒水平后，我们发现miR-135 b与FOXO 1呈负相关。此外，miR-135 b通过exosomes被递送到肿瘤细胞中，以发挥其对GC中血管生成的影响。含有外来体的细胞共培养物和肿瘤植入小鼠模型分别用于体外和体内研究。我们发现来源于GC细胞的miR-135 b抑制FOXO 1蛋白的表达并促进血管生长。我们的发现阐明了一种新的信号通路，包括外泌体，miRNA和靶基因，它们为抗血管生成治疗提供了潜在的靶点。
Exosomes, which act as mediators of intercellular communication, are nanoscale membrane vesicles that contain proteins, lipids, mRNAs, and microRNAs (miRNAs). Additionally, exosomes play a significant role in the development of tumors. The robust angiogenesis of gastric cancer (GC) is one of the reasons for its rampant growth. Drugs and other treatments are not good solutions for the problem of angiogenesis in GC. Here we found that exosome-delivered miRNA contributes greatly to angiogenesis in GC. The downregulation of forkhead box O1 (FOXO1) was observed in GC. After measurement of lentivirus overexpressing microRNA-135b (miR-135b) levels, we found that miR-135b and FOXO1 are negatively correlated. In addition, miR-135b was delivered to tumor cells by exosomes to take its effect on angiogenesis in GC. Exosome-containing cell cocultures and a tumor-implanted mouse model were used for in vitro and in vivo studies, respectively. We showed that miR-135b derived from GC cells suppressed the expression of FOXO1 protein and enhanced the growth of blood vessels. Our findings illustrate a novel signaling pathway comprising exosomes, miRNAs, and target genes, and they provide potential targets for anti-angiogenic therapy.