Hsa_circ_0090002 regulates miR-186-5p/HECTD1 axis to mediate brain microvascular endothelial cell dysfunction

Ischemic injury is a common nervous disease associated with the dysfunction of human brain microvascular endothelial cells (HBMECs). Circular RNAs (circRNAs) have key roles in ischemic injury. This research aims to investigate the role and mechanism of circ_0090002 in ischemic injury. HBMECs were stimulated by oxygen-glucose deprivation (OGD). Circ_0090002, microRNA-186-5p (miR-186-5p), and homologous to the E6-AP Carboxyl Terminus domain E3 ubiquitin ligase 1 (HECTD1) levels were detected by quantitative reverse transcription polymerase chain reaction or Western blotting. Cell viability and migration were determined using Cell Counting Kit-8 (CCK-8) assay and wound healing assay. Flow cytometry and caspase-3 activity assay were used for apoptosis analysis. The oxidative injury and cell toxicity were assessed by reactive oxygen species (ROS) and lactic dehydrogenase (LDH) release assay kits, respectively. The interaction was investigated by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. In vivo assay was performed in rats. Circ_0090002 expression was reduced in OGD-stimulated HBMECs. Circ_0090002 overexpression attenuated OGD-induced reduction of cell viability and migration but elevation of apoptosis, oxidative stress and cell toxicity. Circ_0090002 sponged miR-186-5p and miR-186-5p overexpression reversed the protective role of circ_0090002 against the OGD-induced cell injury. MiR-186-5p targeted HECTD1miR-186-5p knockdown mitigated cell damages in by increasing HECTD1 level in OGD-treated HBMECs. Circ_0090002 could upregulate the HECTD1 expression via regulating miR-186-5p. Circ_0090002 inhibited infarct volume of brain in rats. These results demonstrated that circ_0090002 mitigated OGD-induced cell dysfunction in HBMECs by targeting the miR-186-5p/HECTD1 axis. •Hsa_circ_0090002 abundance is decreased in OGD-stimulated HBMECs.•Hsa_circ_0090002 attenuates OGD-induced inhibition of viability and migration and promotion of apoptosis.•Hsa_circ_0090002 regulates HECTD1 via miR-186-5p.•Hsa_circ_0090002 protects against OGD-induced injury by modulating miR-186-5p.•MiR-186-5p knockdown mitigates OGD-induced injury via targeting HECTD1.