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Down-regulation of UBA6 exacerbates brain injury by inhibiting the activation of Notch signaling pathway to promote cerebral cell apoptosis in rat acute cerebral infarction model.

Abstract：

: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.

journal_name

Mol Cell Probes

journal_title

Molecular and cellular probes

authors

Chen Z,Liu J,Chen Q,Su M,Lu H,Yang Y,Zhou G,Zhang X,Liu Y,Dong W,Fang Q

doi

10.1016/j.mcp.2020.101612

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

101612

eissn

0890-8508

issn

1096-1194

pii

S0890-8508(20)30072-4

journal_volume

pub_type

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Down-regulation of UBA6 exacerbates brain injury by inhibiting the activation of Notch signaling pathway to promote cerebral cell apoptosis in rat acute cerebral infarction model.