Du Jiang, Liang Yuan, Li Ji, Zhao Jin-Ming, Lin Xu-Yong
Department of Pathology, The First Affiliated Hospital and College of Basic Medical Science, China Medical University, Shenyang, China.
Medical Oncology Department of Thoracic Cancer (2), Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China.
Front Oncol. 2020 Mar 13;10:326. doi: 10.3389/fonc.2020.00326. eCollection 2020.
Hypoxia-exposed lung cancer-released exosomal microRNA-23a (miR-23a) has been shown to enhance angiogenesis as well as vascular permeability, contributing to the close correlation between exosomal miR-23a and tumorigenesis. The current study aimed to investigate whether gastric cancer (GC) cell-derived exosomal miR-23a could induce angiogenesis and to elucidate the potential mechanisms associated with the process. Differentially expressed miRNAs in GC were initially screened from the Gene Expression Omnibus database. Target genes were selected following miRNA-mRNA prediction and subsequently verified by dual luciferase reporter assay. RT-qPCR was conducted to detect miR-23a and PTEN expression in GC tissues, cells and exosomes. Human umbilical venous endothelial cells (HUVECs) were co-cultured with GC cell-derived exosomes to assess the angiogenesis mediated by exosomes . Additionally, PTEN was overexpressed in HUVECs to analyze the mechanism by which miR-23a regulates angiogenesis. miR-23a was highly expressed in GC tissues and cells and GC cell-derived exosomes. Angiogenesis was promoted by the co-culture of HUVECs and GC cells-derived exosomes, as evidenced by the increased expression of VEGF but decreased expression of TSP-1. PTEN was targeted by miR-23a and was lowly expressed in GC tissues. In a co-culture system, miR-23a carried by GC cells-derived exosomes promoted angiogenesis via the repression of PTEN. Collectively, GC cell-derived exosomal miR-23a could promote angiogenesis and provide blood supply for growth of GC cells. This study contributes to advancement of miRNA-targeted therapeutics.
缺氧暴露的肺癌释放的外泌体微小RNA-23a（miR-23a）已被证明可增强血管生成以及血管通透性，这促成了外泌体miR-23a与肿瘤发生之间的密切关联。本研究旨在探讨胃癌（GC）细胞衍生的外泌体miR-23a是否可诱导血管生成，并阐明与该过程相关的潜在机制。首先从基因表达综合数据库中筛选出GC中差异表达的微小RNA。通过微小RNA-信使核糖核酸预测选择靶基因，随后通过双荧光素酶报告基因检测进行验证。进行逆转录定量聚合酶链反应以检测GC组织、细胞和外泌体中miR-23a和PTEN的表达。将人脐静脉内皮细胞（HUVECs）与GC细胞衍生的外泌体共培养，以评估外泌体介导的血管生成。此外，在HUVECs中过表达PTEN以分析miR-23a调节血管生成的机制。miR-23a在GC组织、细胞和GC细胞衍生的外泌体中高表达。HUVECs与GC细胞衍生的外泌体共培养促进了血管生成，血管内皮生长因子（VEGF）表达增加但血小板反应蛋白-1（TSP-1）表达降低证明了这一点。PTEN是miR-23a的靶标，在GC组织中低表达。在共培养系统中,GC细胞衍生的外泌体携带的miR-23a通过抑制PTEN促进血管生成。总体而言，GC细胞衍生的外泌体miR-23a可促进血管生成并为GC细胞生长提供血液供应。本研究有助于推进微小RNA靶向治疗。
