LAUSR

BACKGROUND Cerebral ischemia/reperfusion (I/R) injury which leads to neurons damage, is one of the major causes for morbidity. Currently, the underlying mechanisms remain largely elusive. METHODS This study aimed to investigate the role of long non-coding RNA PVT1 in I/R-induced cerebral injury. We established a middle cerebral artery occlusion (MCAO)/reperfusion in vivo mouse model and an in vitro oxygen glucose deprivation (OGD)/reoxygenation (RX) mice neuron cell model. RESULTS Results demonstrated that expressions of PVT1 were significantly induced under I/R. Inhibiting PVT1 effectively alleviated the OGD/RX-mediated neuron cell injury. In addition, we observed the TLR4/MyD88 inflammatory pathway was upregulated by OGD/RX. Bioinformatics analysis, RNA pull-down and luciferase assay demonstrated that PVT1 downregulated miR-187-3p by sponging it in neuron cells. Overexpression of miR-187-3p remarkedly attenuated the OGD/RX-induced neuron cell injury. Western blot, luciferase assay and rescue experiments consistently unveiled that miR-187-3p protected neuron injury by direct targeting MyD88 during the OGD/RX-induced apoptosis. Finally, we demonstrated that restoration of miR-187-3p in PVT1-overexpressing neuron cells successfully recovered the PVT1-promoted neuron injury under OGD/RX through targeting MyD88. CONCLUSION Summarily, these results revealed essential roles and molecular mechanisms of the PVT1-mediated neuron injury under I/R, suggesting that PVT1 could be a promising molecular target for anti-cerebral I/R injury therapy.