Up-regulating lncRNA OIP5-AS1 protects neuron injury against cerebral hypoxia-ischemia induced inflammation and oxidative stress in microglia/macrophage through activating CTRP3 via sponging miR-186-5p

Inflammation and oxidative stress is closely associated with the development of ischemic brain stroke. Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1), a novel identified long non-coding RNA (lncRNA), has been suggested to play an important role in the development of many types of human cancers. However, the functional involvement of OIP5-AS1 in ischemic stroke is still unknown. Quantitative real-time polymerase chain reaction and /or western blot were conducted to determine the expression profiles of OIP5-AS1, C1q/TNF-related protein 3 (CTRP3) and miR-186-5p in the serum of stroke patients, as well as in the ischemic penumbra of rats with middle cerebral artery occlusion/reperfusion (MCAO/R) injury and microglial cells treated with oxygen glucose deprivation/re-oxygenation (OGD/R). Upon selective regulation of OIP5-AS1 and miR-186-5p, the inflammation and oxidative stress responses in microglia/macrophage as well as neurologic functions in MCAO/R rats were detected. Furthermore, the interactions between OIP5-AS1 and miR-186-5p, miR-186-5p and CTRP3 were investigated by RNA immunoprecipitation (RIP) assay, luciferase report assay and bioinformation anaylsis. We observed markedly increased infarct volume, neuronal apoptosis, inflammation and oxidative stress responses in the infarcted lesions of MCAO/R rats, in line with down-regulated levels of OIP5-AS1 and CTRP3 while up-regulated miR-186-5p. Functional studies demonstrated that up-regulation of OIP5-AS1 attenuated infarct volume, neuronal apoptosis, microglia/macrophage inflammation and oxidative stress responses induced by MCAO/R or OGD/R. In terms of mechanism, we revealed that OIP5-AS1-miR-186-5p-CTRP3 axis played a vital role in modulating microglia/macrophage activation and neuronal apoptosis. Up-regulating lncRNA OIP5-AS1 protects neuron injury against MCAO/R induced inflammation and oxidative stress in microglia/macrophage through activating CTRP3 via sponging miR-186-5p.