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.

HIGHLIGHTS

1. CircFKBP3 expression is elevated in OGD-treated HBMECs.

2. OGD-induced HBMEC function loss and inflammation are alleviated by circFKBP3 absence.

3. CircFKBP3 directly targets miR-766-3p to regulate TRAF3 expression.

Keywords:

• CircFKBP3
• miR-766-3p
• TRAF3
• OGD
• HBMEC
• ischemic stroke

Acknowledgement

All patients are aware of, and have consented to take part in this work.

Authors’ contribution

Conceptualization and Methodology: Wei Cheng, Xudong Wang and Zhixin Li; Formal analysis and Data curation: Wenyan Wang, Wei Cheng and Jinli Gao: Wei Cheng and Xudong Wang; Writing – original draft preparation and Writing – review and editing Wenyan Wang, Wei Cheng and Xudong Wang; Approval of final manuscript: all authors

Consent for publication

Patients agree to participate in this work

Disclosure statement

No potential conflict of interest was reported by the authors.

Availability of data and materials

The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.

Additional information

Funding

No funding was received.