MicroRNA-424 suppresses the proliferation of hemangioma-derived endothelial cells by targeting VEGFR-2
MicroRNA-424 suppresses the proliferation of hemangioma-derived endothelial cells by targeting VEGFR-2
复制标题
MicroRNA-424通过靶向VEGFR-2抑制血管瘤来源的内皮细胞的增殖
DOI：
10.3892/mmr.2018.9409
复制
发表时间：
2018-10-01
影响因子：
3.4
通讯作者：
Ou, Jingmin
中科院分区：
文献类型：
--
作者：
Fei, Zhewei;Qiu, Mingke;Ou, Jingmin
血管瘤（HA）是一种常见于婴儿期的良性肿瘤。HA的主要特征是血管内皮细胞的异常增殖。迄今为止，HA的发病机制仍不清楚。充分了解HA肿瘤发生的过程对于开发HA的新治疗方法至关重要。微RNA（miRNAs/miR）的失调已被报道参与多种疾病的发展，包括HA。在本研究中，miR-424在HA衍生的内皮细胞（HemEC）中的表达降低。为了阐明miR-424在HA发生中的作用，本研究在HemEC中过表达或抑制miR-424，揭示miR-424过表达显著抑制HemEC生长并促进凋亡，而miR-424的下调促进细胞生长并抑制细胞凋亡。为了阐明其潜在机制，进行了生物信息学分析，其结果表明，血管内皮生长因子受体2（VEGFR-2）的3-非翻译区可能是miR-424的靶点。双荧光素酶报告基因检测结果证实miR-424抑制VEGFR-2的表达。此外，HemECs中蛋白激酶B（AKT）和细胞外信号调节激酶（ERK）的过度磷酸化以及miR-424的恢复显著抑制了AKT和ERK的激活。总之，这些结果表明miR-424可以靶向VEGFR-2并抑制HemEC生长，并且miR-424在HemEC中的低表达可能导致细胞生长增加和细胞凋亡减少。因此，提出miR-424可作为HemEC中的肿瘤抑制因子，并且VEGFR-2可作为HemEC中的潜在肿瘤抑制靶标并用于治疗HA。
Hemangioma (HA) is a type of benign tumor common in infancy. The main feature of HA is the abnormal proliferation of vascular endothelial cells. To date, the pathogenesis of HA remains unclear. Fully understanding the process of HA tumorigenesis is essential for developing novel treatment for HAs. Dysregulation of microRNAs (miRNAs/miR) has been reported to be involved in the development of various diseases, including HA. In the present study, the expression of miR-424 decreased in HA-derived endothelial cells (HemECs). To elucidate the role of miR-424 in HAs development, the present study overexpressed or inhibited miR-424 in HemECs, revealing that miR-424 overexpression significantly inhibited HemEC growth and promoted apoptosis, while the downregulation of miR-424 promoted cell growth and inhibited cell apoptosis. To elucidate the underlying mechanism, bioinformatic analyses were performed, the result of which demonstrated that the 3-untranslated region of vascular endothelial growth factor receptor 2 (VEGFR-2) may be a target of miR-424. The result of a dual luciferase reporter assay confirmed that the expression of VEGFR-2 was inhibited by miR-424. In addition, it was revealed that the hyper-phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) in HemECs, and the restoration of miR-424 markedly inhibited the activation of AKT and ERK. In conclusion, these results indicated that miR-424 may target VEGFR-2 and inhibit HemECs growth, and that low expression of miR-424 in HemECs may lead to an increase in cell growth and a decrease in cell apoptosis. Thus, it was proposed that miR-424 may serve as a tumor suppressor in HemECs, and that VEGFR-2 may be a potential tumor suppressive target in HemECs and for the treatment of HA.