Department of Dermatology, Zhejiang Provincial People's Hospital, Hangzhou, China.
Department of Dermatology, Zhejiang Provincial People's Hospital, Hangzhou, China,
Cerebrovasc Dis. 2020;49(5):462-473. doi: 10.1159/000508302. Epub 2020 Sep 2.
Hemangioma (Hem) is a benign tumor commonly seen in infancy with a relative high morbidity. Human umbilical vein endothelial cell (HUVEC)-derived extracellular vesicles (EVs) are actively participated in Hem. Therefore, this study is designed to figure out the underlying mechanism of HUVEC-derived EVs in Hem.
Initially, EVs were separated from HUVECs and identified. HUVEC-derived EVs in normoxia or hypoxia were then cultivated with Hem endothelial cells (HemECs) to test the proliferation, apoptosis, and migration of HemECs. Microarray analysis was performed to select microRNAs (miRs) with differential expression. miR-210 in hypoxia-induced HUVECs was silenced, and the relevant EVs were extracted and then co-cultured with HemECs to perform biological effect experiments. Then, the target relation between miR-210 and homeobox A9 (HOXA9) was identified by the dual luciferase reporter gene assay and RNA immunoprecipitation assay. Moreover, xenograft transplantation was also applied to confirm the in vitro experiments.
Hypoxia-induced HUVECs promoted release of EVs, which were absorbed by HemECs. Hypoxia-induced HUVEC-EVs promoted HemEC proliferation and migration and inhibited apoptosis. miR-210 from the hypoxia-induced HUVEC-EVs was highly expressed and promoted HemEC growth. Silencing miR-210 expression in the hypoxia-induced HUVEC-EVs suppresses Hem development in vivo. In addition, miR-210 targeted HOXA9.
Silencing miR-210 in HUVEC-derived EVs could suppress Hem by targeting HOXA9. This investigation may provide novel insights for Hem treatment.
血管瘤（Hem）是一种常见的婴儿期良性肿瘤，发病率相对较高。人脐静脉内皮细胞（HUVEC）衍生的细胞外囊泡（EVs）积极参与 Hem 的发生。因此，本研究旨在探讨 HUVEC 衍生 EVs 在 Hem 中的潜在作用机制。
首先，从 HUVEC 中分离并鉴定 EVs。然后将常氧或缺氧条件下的 HUVEC 衍生 EVs 与 Hem 内皮细胞（HemECs）共培养，检测 HemECs 的增殖、凋亡和迁移。进行微阵列分析以筛选差异表达的 microRNAs（miRs）。沉默缺氧诱导的 HUVEC 中的 miR-210，并提取相关 EVs 与 HemECs 共培养，进行生物学效应实验。然后，通过双荧光素酶报告基因检测和 RNA 免疫沉淀实验鉴定 miR-210 与同源盒 A9（HOXA9）之间的靶关系。此外，还进行了异种移植移植实验以验证体外实验结果。
缺氧诱导的 HUVEC 促进 EVs 的释放，这些 EVs 被 HemECs 吸收。缺氧诱导的 HUVEC-EVs 促进 HemEC 增殖、迁移并抑制凋亡。缺氧诱导的 HUVEC-EVs 中的 miR-210 表达上调，并促进 HemEC 生长。沉默缺氧诱导的 HUVEC-EVs 中的 miR-210 表达可抑制体内 Hem 的发育。此外，miR-210 靶向 HOXA9。
沉默 HUVEC 衍生 EVs 中的 miR-210 可通过靶向 HOXA9 抑制 Hem 的发生。该研究为 Hem 的治疗提供了新的思路。
