CircNUFIP2 overexpression induces GDF11 to ameliorate oxygen-glucose deprivation-induced hippocampal neuron cell apoptosis and oxidative stress after cerebral ischemia

Background Previous data have indicated the regulation of circular RNA (circRNA) toward cerebral ischemia. This study aims to reveal the effects of circNUFIP2 on cerebral ischemia and the underlying mechanism. Methods Oxygen-glucose deprivation (OGD) hippocampal neuron (HT22) cell model and middle cerebral artery occlusion (MCAO) mouse model were used for this study. The expression of circRNA nuclear FMR1 interacting protein 2 (circNUFIP2), microRNA-1224-5p (miR-1224-5p) and growth differentiation factor 11 (GDF11) was detected by quantitative real-time polymerase-chain reaction. Protein expression was checked by Western blotting. The binding relationships among circNUFIP2, miR-1224-5p and GDF11 were identified by dual-luciferase reporter assay, RNA pull-down assay, and RNA immunoprecipitation assay. Cell proliferation and apoptosis were investigated by 5-Ethynyl-29-deoxyuridine and flow cytometry analysis, respectively. Results CircNUFIP2 and GDF11 expression were decreased, but miR-1224-5p was increased in OGD-treated HT22 cells when compared with their expression in control groups. OGD treatment inhibited HT22 cell proliferation but induced cell apoptosis and oxidative stress; however, these effects were attenuated after circNUFIP2 overexpression. Also, circNUFIP2 upregulation assuaged the cerebral infarction of MCAO mice. Besides, circNUFIP2 bound to miR-1224-5p and mediated OGD-induced HT22 cell damage through miR-1224-5p. Meanwhile, knockdown of GDF11, a target gene of miR-1224-5p, relieved miR-1224-5p depletion-caused effects in OGD-treated HT22 cells. Furthermore, circNUFIP2 regulated GDF11 expression by interacting with miR-1224-5p. Conclusion CircNUFIP2 overexpression protected neuron cells against cerebral ischemia-induced damage, at least in part, by the miR-1224-5p/GDF11 pathway, providing a possible target for the therapy of cerebral ischemic stroke