LncRNA PEG11as Aggravates Cerebral Ischemia/Reperfusion Injury After Ischemic Stroke Through miR-342-5p /PFN1 Axis

LncRNAs are highly expressed in the CNS and regulate physiological and pathophysiological processes. However, the potential role of lncRNAs in cerebral ischemia/reperfusion (I/R) injury, a common pathological process after ischemic stroke (IS) remains widely unknown. From a RNA-Seq analysis, 254 lncRNAs were identified to be differentially expressed in ischemic/reperfusion (I/R) mice brain tissue, including 234 upregulated and 5 downregulated lncRNAs. Among the 9 lncRNA used for verification, lncRNA paternal expressed gene 11 antisense (PEG11as) was significantly upregulated in the ischemic brain tissues of transient middle cerebral artery occlusion (MCAO) mice and N2a cells from oxygen-glucose deprivation/reoxygenation (OGD/R). Downregulate of PEG11as could markedly attenuate the brain infarct volume, alleviate neurological deficit in vivo, and effectively promote neuron survival, attenuate neuronal apoptosis and caspase 3 activity both in vivo and in vitro. FISH assay discovered that PEG11as was mainly located in the cytoplasm, indicating that PEG11as could be used as a competitive endogenous RNA (ceRNA) to participate in post-transcriptional regulation. Furthermore, we demonstrate PEG11as was able to sponge miR-342-5p to inhibit miR-342-5p activity, resulting in profilin 1 (PFN1) overexpression and subsequently promoting apoptosis. Therefore, this study explored the role and underlying mechanisms of PEG11as in cerebral I/R-induced neuronal damage. It might contribute to the understand of the pathogenesis and provide a potential therapeutic option for the cerebral I/R.