Department of Neurology Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Henan Province Neurological Disease Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Mol Biotechnol. 2024 Oct;66(10):2897-2908. doi: 10.1007/s12033-023-00906-9. Epub 2023 Oct 17.
Angiogenesis promotes neurological recovery after acute ischemic stroke (AIS), and microRNAs play crucial roles in cerebral angiogenesis. This study found that Homo sapiens-microRNA-1303(miR-1303) was reduced in blood specimens of AIS patients and human umbilical vein endothelial cells after suffering from oxygen-glucose deprivation/reperfusion. The experiment detected the effect of miR-1303 on angiogenesis by wound healing assay, tube formation assay, and transwell assay. Down-regulation of miRNA-1303 promotes angiogenesis in vitro experiments, while miR-1303 over-expression reverses this effect. Based on bioinformatics analyses and dual-luciferase reporter assay, the thrombospondin type 1 domain containing 7A (THSD7A) was investigated and further validated as the downstream gene of miR-1303. Furthermore, the knockdown of miR-1303 decreased the protein translation and mRNA transcript levels of THSD7A. Our results reveal a novel miR-1303/THSD7A pathway for angiogenesis and further imply that miR-1303 can be a promising biomarker and therapeutic target for AIS.
血管生成促进急性缺血性脑卒中(AIS)后的神经恢复,而 microRNAs 在脑血管生成中发挥关键作用。本研究发现,AIS 患者的血液标本和缺氧/葡萄糖再灌注后人脐静脉内皮细胞中人类 microRNA-1303(miR-1303)减少。该实验通过划痕愈合试验、管形成试验和 Transwell 试验检测了 miR-1303 对血管生成的影响。miR-1303 的下调促进了体外实验中的血管生成,而 miR-1303 的过表达则逆转了这种作用。基于生物信息学分析和双荧光素酶报告基因检测,研究了血小板反应蛋白 1 型域包含 7A(THSD7A),并进一步验证其为 miR-1303 的下游基因。此外,miR-1303 的敲低降低了 THSD7A 的蛋白翻译和 mRNA 转录水平。我们的结果揭示了一个新的 miR-1303/THSD7A 血管生成途径,并进一步表明 miR-1303 可以作为 AIS 的有前途的生物标志物和治疗靶点。