Feng Nianping, Wang Zhengfei, Zhang Zhuo, He Xijun, Wang Chunlai, Zhang Liming
Department of Neurology, First Clinical Hospital, Harbin Medical University, Harbin 150001, China; Department of Neurology, Second Clinical Hospital, Harbin Medical University, Harbin 150086, China.
Department of Cerebropathy, Qiqihaer City Hospital of Traditional Chinese Medicine, Qiqihaer 161000, China.
Neurosci Lett. 2015 Mar 30;591:1-7. doi: 10.1016/j.neulet.2015.02.002. Epub 2015 Feb 4.
Angiogenesis is essential for recovery from various neurovascular diseases, such as ischemic stroke. Previous studies have revealed the regulatory role of MicroRNAs in angiogenesis in various types of cancer cells. However, the role of miR-487b in angiogenesis and how it regulates the angiogenic process of endothelial cells remain unclear. In this study, we found miR-487b was up-regulated in the plasma of ischemic stroke patients. Further, over-expression of miR-487b enhanced cell proliferation, migration, invasion and tube formation in human umbilical vein endothelial cells. Using bioinformatic analysis, we found a putative binding site of miR-487b in the 3' untranslated regions of Thrombospondin 1 mRNA, an endogenous inhibitor of angiogenesis. This direct binding was confirmed by luciferase assay. These results demonstrate that miR-487b regulates angiogenesis by directly targeting THBS1 in HUVECs, indicating that miR-487b may contribute to angiogenesis and the functional recovery from ischemic stroke. miR-487b could represent a potential therapeutic option for neurovascular disease.
血管生成对于从各种神经血管疾病(如缺血性中风)中恢复至关重要。先前的研究揭示了微小RNA在各种类型癌细胞血管生成中的调节作用。然而,miR-487b在血管生成中的作用以及它如何调节内皮细胞的血管生成过程仍不清楚。在本研究中,我们发现miR-487b在缺血性中风患者的血浆中上调。此外,miR-487b的过表达增强了人脐静脉内皮细胞的增殖、迁移、侵袭和管形成。通过生物信息学分析,我们在血管生成的内源性抑制剂血小板反应蛋白1(THBS1)mRNA的3'非翻译区发现了一个miR-487b的假定结合位点。荧光素酶测定证实了这种直接结合。这些结果表明,miR-487b通过直接靶向人脐静脉内皮细胞中的THBS1来调节血管生成,表明miR-487b可能有助于血管生成和缺血性中风后的功能恢复。miR-487b可能是神经血管疾病的一种潜在治疗选择。