Depleted miR-125a-5p Causes Vascular Endothelial Cell Dysfunction in Deep Vein Thrombosis by Targeting Angiopoietin 2

miR-125a-5p 缺失通过靶向血管生成素 2 导致深静脉血栓形成中的血管内皮细胞功能障碍

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作者:Jianyuan Huang #, Xinning Wu #, Quan Zhang, Lixia Yang, Guozhen Wan, Xiaoqiang Zhang, Ying Wang, Guannan Zhao

Abstract

Deep vein thrombosis (DVT) is a common and fatal disease with a pathology involving endothelial dysfunction. The present research aimed to address the potential clinical significance of miR-125a-5p in DVT and its effect on the dysfunction of Human umbilical vein endothelial cells (HUVECs). Serum miR-125a-5p levels were measured using RT-qPCR in 88 patients with DVT and 76 healthy controls. ROC was plotted to evaluate the diagnostic potential of miR-125a-5p. Spearman's correlation coefficient was performed to calculate the correlation between miR-125a-5p and clinical indicators. CCK-8, Transwell, and ELISA were employed to verify the effects of cell proliferation, migration, and inflammatory and adhesion molecules. Dual-luciferase reporter assay to analyze potential target for miR-125a-5p. Serum miR-125a-5p was reduced in patients with DVT compared with healthy controls (P < 0.001). ROC showed that miR-125a-5p significantly identified patients with DVT from the healthy controls (AUC = 0.834). Furthermore, serum miR-125a-5p was negatively correlated with inflammatory factors and coagulation factors. In in vitro studies, proliferation and migration of HUVECs were inhibited by suppressed miR-125a-5p, whereas inflammation and adhesion factors were considerably promoted (P < 0.05). Moreover, miR-125-5p directly targeted the 3'UTR of angiopoietin 2 (ANGPT2) and was negatively regulated. Finally, serum ANGPT2 was elevated in patients with DVT and was negatively correlated with serum miR-125a-5p. The current research demonstrated that decreased miR-125a-5p was a novel potential diagnostic biomarker for DVT and that it may be involved in DVT progression by targeting ANGPT2 to regulate endothelial dysfunction.

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