CircFKBP3 absence alleviates oxygen glucose deprivation-induced function loss of human brain microvascular endothelial cells in vitro via governing the miR-766-3p/TRAF3 axis.

Abstract

BACKGROUND:

Brain microvascular endothelial cell (BMEC) functions loss is a key event in the development of ischemic stroke, which may be affected by the dysregulation of circular RNAs (circRNAs). We aimed to unveil the role of circRNA FKBP Prolyl Isomerase 3 (circFKBP3) in cell models of ischemic stroke.

METHODS:

Cell models of ischemic stroke were constructed in human BEMCs (HBMECs) with the treatment of oxygen glucose deprivation (OGD). Quantitative real-time PCR (qPCR) and western blotting were conducted for expression analysis of circFKBP3, miR-766-3p and TNF receptor associated factor 3 (TRAF3). CCK-8, transwell, wound healing, flow cytometry, tube formation and ELISA assays were implemented to monitor cell viability, migration, apoptosis, angiogenesis and inflammation production. The putative binding relationship between miR-766-3p and circFKBP3 or TRAF3 was validated by dual-luciferase, RIP and pull-down assays.

RESULTS:

CircFKBP3 expression was elevated in OGD-treated HBMECs. OGD suppressed HBMEC viability, migration, angiogenesis, and provoked cell apoptosis and inflammation production, while knockdown of circFKBP3 attenuated these effects. CircFKBP3 interacted with miR-766-3p, and circFKBP3 absence-repressed HBMEC function loss and inflammation were recovered by miR-766-3p inhibition. CircFKBP3 targeted miR-766-3p to regulate TRAF3 expression. MiR-766-3p enrichment-repressed HBMEC function loss and inflammation were recovered by TRAF3 overexpression.

CONCLUSION:

CircFKBP3 absence alleviated OGD-induced function loss and inflammatory responses of HBMECs via governing the miR-766-3p/TRAF3 axis.

• Authors: Wenyan Wang, Wei Cheng, Xudong Wang, Zhixin Li, Jinli Gao
• Journal: The International journal of neuroscience (Int J Neurosci) Pg. 1-30 (Nov 20 2023) ISSN: 1563-5279 [Electronic] England
• PMID: 37982234 (Publication Type: Journal Article)