Depletion of circ_0006459 protects human brain microvascular endothelial cells from oxygen-glucose deprivation-induced damage through the miR-940/FOXJ2 pathway |
| |
| Institution: | 1. Hospital of LMU Munich, Division of General, Visceral, Vascular and Transplant Surgery, Munich, Bavaria, Germany;2. Hospital of LMU Munich, Division of Nephrology, Department of Medicine IV, Munich, Bavaria, Germany;3. University Hospital Cologne, Department for General, Visceral, Cancer and Transplant Surgery, Cologne, North Rhine-Westphalia, Germany;1. Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai 200433, People''s Republic of China;2. Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA;1. Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, China;2. Gansu Province Clinical Research Center for Urology, Lanzhou, China;3. Second Clinical School, Lanzhou University, Lanzhou, China;1. Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China;2. Department of Nephrology, University-Town Hospital of Chongqing Medical University, Chongqing 401331, China;3. Science and Technology Innovation Center of Jiangjin District, Chongqing 402260, China;1. Department of Surgery, Division of Transplantation, SUNY Upstate Medical University, Syracuse, NY, USA;2. Department of Pathology and Laboratory Medicine, SUNY Upstate Medical University, Syracuse, NY, USA;3. Norton College of Medicine, SUNY Upstate Medical University, Syracuse, NY, USA;1. Wuhan Third Hospital - Hospital of Wuhan University, Wuhan 430060, China;2. Institute of Reproductive Health, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China |
| |
| Abstract: | BackgroundMultiple circular RNAs (circRNAs) play important roles in ischemic stroke. The present study aims to reveal the role and the mechanism of circ_0006459 in ischemic stroke.MethodsHuman brain microvascular endothelial cells (HBMECs) were treated with oxygen-glucose deprivation (OGD) to mimic an in vitro ischemic stroke model. RNA expression of circ_0006459, microRNA-940 (miR-940), and forkhead box J2 (FOXJ2) was detected by quantitative real-time polymerase chain reaction. Cell proliferation was analyzed by cell counting kit-8 (CCK-8) and 5-Ethynyl-29-deoxyuridine (EdU) assays. Cell apoptotic rate was quantified by flow cytometry analysis. The protein expression of proliferating cell nuclear antigen (PCNA), clusters of differentiation 6 (CDK6), BCL2-associated x protein (Bax), B-cell lymphoma 2 (Bcl2), interleukin-1β (IL-1β), IL-8, IL-18 and tumor necrosis factor-α (TNF-α) was analyzed by Western blotting. The regulatory relationships among circ_0006459, miR-940, and F 《人生只有一件事》 OXJ2 were identified by dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA pull-down assay.ResultsCirc_0006459 and FOXJ2 expression were significantly upregulated, whereas miR-940 expression was downregulated in HBMECs after OGD. Circ_0006459 depletion assuaged OGD-induced inhibition in cell proliferation and promotion in cell apoptosis and inflammation in HBMECs. Circ_0006459 acted as a sponge for miR-940, and miR-940 targeted FOXJ2 in HBMECs. Besides, miR-940 silencing or FOXJ2 overexpression relieved circ_0006459 knockdown-induced promotion in cell proliferation and inhibition in cell apoptosis and inflammation in OGD-induced HBMECs. Further, circ_0006459 depletion decreased FOXJ2 protein expression by interacting with miR-940.ConclusionDepletion of circ_0006459 protected human brain microvascular endothelial cells from oxygen-glucose deprivation-induced damage through miR-940/FOXJ2 pathway, providing a promising therapeutic target for ischemic stroke. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
