OBJECTIVE Circular RNAs(circRNAs) are highly expressed in the brain and involved in various central nervous system diseases.However,the potential role of circRNAs in ischemic brain injury remains largely unknown.The present study investigated the functional significance of a circular RNA TLK1(circTLK1) in cerebral ischemic injury.METHODS The expression of circTLK1,neurological deficit scores,infarct volume,and long-term neurological deficits were examined in a rodent model of middle cerebral artery occlusion using real-time polymerase chain reaction,triphenyltetrazolium chloride staining,magnetic resonance imaging,GolgiCox staining and behavior tests.Neuronal injury was undertaken in primary cultured cortical neurons challenged by oxygen-glucose deprivation using Western blotting and immunostaining.The interaction between circTLK1 and miR-335-3 p was examined using fluorescence in situ hybridization and affinity isolation assay.The downstream target of miR-335-3 p-TIPARP was determined by luciferase assay and Western blotting assay.RESULTS CircTLK1 levels were significantly increased in brain tissues in a mouse model of focal cerebral ischemia and reperfusion.Knockdown of circTLK1 expression significantly decreased infarct volumes,attenuated neuronal injury,and improved subsequent long-term neurological deficits.Furthermore,circT LK1 functions as an endogenous microRNA-335-3 p sponge to inhibit miR-335-3 p activity,resulting in the inhibition of 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible polymerase expression and subsequent attenuation of neuronal injury.Clinical studies confirmed the up-regulation of circT LK1 in plasma of patients with ischemic stroke.CONCLUSION CircTLK1 and its underlying mechanisms are involved in ischemic brain injury,suggesting circTLK1 as a potential therapeutic target for ischemic stroke.
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