Deng Ting, Zhang Haiyang, Yang Haiou, Wang Huiya, Bai Ming, Sun Wu, Wang Xinyi, Si Yiran, Ning Tao, Zhang Le, Li Hongli, Ge Shaohua, Liu Rui, Lin Dan, Li Shuang, Ying Guoguang, Ba Yi
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
Mol Ther Nucleic Acids. 2020 Mar 6;19:1449-1459. doi: 10.1016/j.omtn.2020.01.024. Epub 2020 Jan 30.
Exosomes, membranous nanovesicles, naturally carry proteins, mRNAs, and microRNAs (miRNAs) and play important roles in tumor pathogenesis. Here we showed that gastric cancer (GC) cell-derived exosomes can function as vehicles to deliver miR-155 to promote angiogenesis in GC. In this study, we first detected that the expression of miR-155 and c-MYB was negatively correlated in GC and that c-MYB was a direct target of miR-155. We next characterized the promotional effect of exosome-delivered miR-155 on angiogenesis and tumor growth in GC. We found that miR-155 could inhibit c-MYB but increase vascular endothelial growth factor (VEGF) expression and promote growth, metastasis, and tube formation of vascular cells, causing the occurrence and development of tumors. We also used a tumor implantation mouse model to show that exosomes containing miR-155 significantly augment the growth rate of the vasculature and tumors in vivo. Our results illustrate the potential mechanism between miR-155 and angiogenesis in GC. These findings contribute to our understanding of the function of miR-155 and exosomes for GC therapy.
外泌体，即膜性纳米囊泡，天然携带蛋白质、信使核糖核酸（mRNA）和微小核糖核酸（miRNA），并在肿瘤发病机制中发挥重要作用。在此我们表明，胃癌（GC）细胞衍生的外泌体可作为载体传递miR-155，以促进胃癌中的血管生成。在本研究中，我们首先检测到在胃癌中miR-155与c-MYB的表达呈负相关，且c-MYB是miR-155的直接靶点。接下来，我们对通过外泌体传递的miR-155在胃癌血管生成和肿瘤生长中的促进作用进行了表征。我们发现，miR-155可抑制c-MYB，但增加血管内皮生长因子（VEGF）的表达，并促进血管细胞的生长、转移和管腔形成，从而导致肿瘤的发生和发展。我们还使用肿瘤植入小鼠模型表明，含有miR-155的外泌体在体内可显著提高血管系统和肿瘤的生长速率。我们的结果阐明了miR-155与胃癌血管生成之间的潜在机制。这些发现有助于我们理解miR-155和外泌体在胃癌治疗中的作用。
