This study aimed to examine the UBA6 role in brain injury mediated by acute cerebral infarction (ACI). In order to screen potential therapeutic targets for ACI, two expression profiles, including GSE97537 and GSE97533 datasets, were downloaded from the GEO database. The Venn method to identify the common DEGs. 68 up-regulated overlapping DEGs and 51 down-regulated overlapping DEGs were used to construct the PPI network by STRING online database. UBA6 was identified as a hub gene by the CytoHubba plugin from Cytoscape. GO and KEGG pathway enrichment analyses were conducted using DAVID online website. UBA6 knockout exacerbated MCAO-mediated brain injury and cell apoptosis in rat brain tissues by H&E and TTC staining and TUNEL assay. The results of flow cytometry and western blot assays further demonstrated that UBA6 inhibition induced the apoptosis of hippocampal neurons and increased cleaved-caspase-3/9 protein levels. Notch1, NICD and Hes1 protein levels were suppressed by down-regulated UBA6. UBA6 was lowly expression in poor prognosis group of 100 patients with ACI. Logistic regression analysis indicated that hypertension, blood glucose, urokinase dose, UBA6 expression and AF were the main risk factors of poor prognosis after thrombolytic therapy for patients with ACI. The ROC curve analysis showed that the sensitivity and specificity of UBA6 was good (sensitivity 100%, specificity 89%, and AUC = 0.772) to be used to evaluate the poor prognosis of ACI. In conclusion, down-regulated UBA6 intensified MCAO-induced brain injury by inhibiting the activation of Notch signaling pathway to promote the apoptosis of hippocampal neurons and was used to predict the poor prognosis of ACI.

本研究旨在检查 UBA6 在急性脑梗死 (ACI) 介导的脑损伤中的作用。为了筛选 ACI 的潜在治疗靶点，从 GEO 数据库下载了两个表达谱，包括 GSE97537 和 GSE97533 数据集。识别常见 DEG 的维恩方法。STRING在线数据库使用68个上调重叠DEG和51个下调重叠DEG构建PPI网络。UBA6 被 Cytoscape 的 CytoHubba 插件鉴定为一个集线器基因。使用 DAVID 在线网站进行 GO 和 KEGG 通路富集分析。通过 H&E 和 TTC 染色和 TUNEL 测定，UBA6 敲除加剧了大鼠脑组织中 MCAO 介导的脑损伤和细胞凋亡。流式细胞术和蛋白质印迹分析的结果进一步证明 UBA6 抑制诱导海马神经元凋亡并增加 cleaved-caspase-3/9 蛋白水平。Notch1、NICD 和 Hes1 蛋白水平被下调的 UBA6 抑制。UBA6在100例ACI患者预后不良组中低表达。Logistic回归分析表明高血压、血糖、尿激酶剂量、UBA6表达和房颤是ACI患者溶栓治疗后预后不良的主要危险因素。ROC曲线分析显示UBA6的敏感性和特异性较好（敏感性100%，特异性89%，AUC=0.772），可用于评估ACI的不良预后。综上所述，