Zhang Pin-Jing, Luo Chen, Chen Jinli, Yang Jing, Wu Quan, Chen Lilong, Wang Hui, Wu Junfeng, Zhang Hai-Feng
Department of Neurosurgery, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning, China.
Department of Neurosurgery, The First People's Hospital of Jiashan, 314100 Zhejiang, China.
Neuroscience. 2025 Mar 17;569:114-122. doi: 10.1016/j.neuroscience.2025.01.060. Epub 2025 Jan 31.
Hypertension is a common risk factors for ischemic stroke (IS), with the widely involvement of long non-coding RNAs (lncRNAs). The expression pattern and clinical significance of lncRNA PSMB8-AS1 was examined in essential hypertension (EH) patients with or without IS, as well as its role and mechanism in IS-induced neuron cell injury. Serum PSMB8-AS1 levels in 260 EH cases without IS and 280 participants with IS were detected via reverse transcription - quantitative polymerase chain reaction (RT-qPCR). The outcome during 12-month follow-up period was recorded. Receiver operating characteristic (ROC) curve and Kaplan - Meier (K-M) plot were drawn to evaluate diagnostic and prognostic values. HT22 cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) condition for cell function experiments. The cell viability, apoptosis, and inflammatory response were detected. Elevated expression of PSMB8-AS1 can differentiate IS from EH patients, and was independently related to the poor functional prognosis. Patients with high PSMB8-AS1 expression were likely to relapse during the 12-month follow-up period. In vitro, PSMB8-AS1 knockdown attenuated OGD/R-induced neuron cell apoptosis and inflammatory response, which was returned by microRNA-22-3p downregulation. PI3K-Akt signaling was of significance during the progress based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. PSMB8-AS1 acts as a novel biomarker for the diagnosis of IS in EH patients. Elevated PSMB8-AS1 is associated with worse neurological outcomes and higher recurrence rates of IS patients. LncRNA PSMB8-AS1 knockdown might have a promising role in attenuating OGD/R-induced neuron cell injury, that might be related to miR-22-3p.
高血压是缺血性卒中（IS）的常见危险因素，长链非编码RNA（lncRNA）广泛参与其中。本研究检测了lncRNA PSMB8-AS1在有或无IS的原发性高血压（EH）患者中的表达模式及临床意义，以及其在IS诱导的神经元细胞损伤中的作用和机制。通过逆转录-定量聚合酶链反应（RT-qPCR）检测了260例无IS的EH患者和280例IS患者的血清PSMB8-AS1水平。记录12个月随访期内的结果。绘制受试者工作特征（ROC）曲线和Kaplan-Meier（K-M）图以评估诊断和预后价值。将HT22细胞置于氧糖剥夺/复氧（OGD/R）条件下进行细胞功能实验。检测细胞活力、凋亡和炎症反应。PSMB8-AS1表达升高可区分EH患者中的IS，且与不良功能预后独立相关。PSMB8-AS1表达高的患者在12个月随访期内可能复发。在体外，敲低PSMB8-AS1可减轻OGD/R诱导的神经元细胞凋亡和炎症反应，而这一作用可通过下调微小RNA-22-3p恢复。基于京都基因与基因组百科全书（KEGG）分析，PI3K-Akt信号通路在这一过程中具有重要意义。PSMB8-AS1作为一种新型生物标志物可用于诊断EH患者中的IS。PSMB8-AS1升高与IS患者更差的神经学结局和更高的复发率相关。敲低lncRNA PSMB8-AS1可能在减轻OGD/R诱导的神经元细胞损伤方面具有潜在作用，这可能与miR-22-3p有关。
