Reveal the correlation between hub hypoxia/immune-related genes and immunity and diagnosis, and the effect of SAP30 on cell apoptosis, ROS and MDA production in cerebral ischemic stroke

Aging (Albany NY). 2023 Dec 27;15(24):15161-15182. doi: 10.18632/aging.205339. Epub 2023 Dec 27.

Abstract

Background: Cerebral ischemic stroke (CIS) is a common cerebrovascular disease. The purpose of this study was to investigate the potential mechanism of hypoxia and immune-related genes in CIS.

Methods: All data were downloaded from public databases. Hub mRNAs was identified by differential expression analysis, WGCNA analysis and machine learning. Hub mRNAs were used to construct the classification models. Pearson correlation analysis was used to analyze the correlation between hub mRNAs and immune cell infiltration. Finally, the SAP30 was selected for verification in HMC3 cells.

Results: The SVM, RF and DT classification models constructed based on 6 hub mRNAs had higher area under the curve values, which implied that these classification models had high diagnostic accuracy. Pearson correlation analysis found that Macrophage has the highest negative correlation with CCR7, while Neutrophil has the highest positive correlation with SLC2A3. Drug prediction found that ruxolitinib, methotrexate, resveratrol and resatorvid may play a role in disease treatment by targeting different hub mRNAs. Notably, inhibition of SAP30 expression can reduce the apoptosis of HMC3 cells and inhibit the production of ROS and MDA.

Conclusion: The identification of hub miRNAs and the construction of classification diagnosis models provide a theoretical basis for the diagnosis and management of CIS.

Keywords: SAP30; cerebral ischemic stroke; hypoxia; immune.

MeSH terms

  • Apoptosis / genetics
  • Histone Deacetylases
  • Humans
  • Hypoxia
  • Ischemic Stroke* / diagnosis
  • Ischemic Stroke* / genetics
  • Malondialdehyde / metabolism
  • Reactive Oxygen Species
  • Stroke* / genetics

Substances

  • Histone Deacetylases
  • Reactive Oxygen Species
  • SAP30 protein, human
  • Malondialdehyde