LncRNA Taurine Up-Regulated 1 Knockout Provides Neuroprotection in Ischemic Stroke Rats by Inhibiting Nuclear-Cytoplasmic Shuttling of HuR

Abstract

Background: Long non-coding RNA taurine-upregulated gene 1 (TUG1) is involved in various cellular processes, but its role in cerebral ischemia–reperfusion injury remains unclear. This study investigated TUG1’s role in regulating the nucleocytoplasmic shuttling of human antigen R (HuR), a key apoptosis regulator under ischemic conditions. Methods: CRISPR-Cas9 technology was used to generate TUG1 knockout Sprague Dawley rats to assess TUG1’s impact on ischemic injury. The infarct area and neuronal apoptosis were evaluated using TUNEL, hematoxylin and eosin (HE), and TTC staining, while behavioral functions were assessed. Immunofluorescence staining with confocal microscopy was employed to examine TUG1-mediated HuR translocation and expression changes in the apoptosis-related proteins COX-2 and Bax. Results: TUG1 knockout rats showed significantly reduced cerebral infarct areas, decreased neuronal apoptosis, and improved neurological functions compared to controls. Immunofluorescence staining revealed that HuR translocation from the nucleus to the cytoplasm was inhibited, leading to decreased COX-2 and Bax expression levels. Conclusions: TUG1 knockout reduces ischemic damage and neuronal apoptosis by inhibiting HuR nucleocytoplasmic shuttling, making TUG1 a potential therapeutic target for ischemic stroke.