FOXP3-regulated LncRNA SNHG17 prevents cerebral ischemia-reperfusion injury by targeting CYP2J2

Ischemic stroke is associated with the highest disability rate worldwide, severely impacting the quality of life for patients and their caregivers/families. Long non-coding RNAs (lncRNAs) play multiple roles in cerebrovascular diseases, but the function and regulatory mechanisms of lncRNA SNHG17 in ischemic stroke remain unclear. Clinical blood samples from acute ischemic stroke patients and healthy individuals were analyzed to assess SNHG17 expression. In vitro oxygen-glucose deprivation/reoxygenation (OGD/R) models using human cerebral microvascular endothelial cells (HCMECs) and in vivo middle cerebral artery occlusion/reperfusion (MCAO/R) models in mice were established to evaluate SNHG17 expression under ischemic conditions. Molecular analyses, including upstream and downstream regulatory investigations, were performed to identify SNHG17's interaction with Forkhead box protein 3 (FOXP3) and Cytochrome P450 Family 2 Subfamily J Member 2 (CYP2J2). Functional assays assessed SNHG17's role in mitophagy, apoptosis, oxidative stress (OS), and mitochondrial dysfunction. SNHG17 expression was significantly reduced in the peripheral blood of acute ischemic stroke patients compared to healthy controls. Similarly, SNHG17 was downregulated in OGD/R-treated HCMECs and MCAO/R mouse models. Molecular studies revealed that FOXP3 transcriptionally regulates SNHG17, and overexpression of SNHG17 mediated mitophagy, suppressed apoptosis, alleviated OS, and mitigated mitochondrial dysfunction. Mechanistically, SNHG17 exerted neuroprotective effects by targeting CYP2J2, which is critical for maintaining endothelial cell function under ischemic stress. This study for the first time demonstrates that SNHG17, regulated by FOXP3, plays a protective role in ischemic stroke by enhancing cell survival, reducing OS, and preserving mitochondrial function via CYP2J2. The findings highlight SNHG17 as a potential therapeutic target and prognostic biomarker for improving outcomes in ischemic stroke patients.