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Published in: European Journal of Medical Research 1/2023

Open Access 01-12-2023 | Stroke | Research

Identification of ANXA3 as a biomarker associated with pyroptosis in ischemic stroke

Authors: Linquan Liu, Yahong Cai, Changqing Deng

Published in: European Journal of Medical Research | Issue 1/2023

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Abstract

Background

Pyroptosis plays an important role in the pathological process of ischemic stroke (IS). However, the exact mechanism of pyroptosis remains unclear. This paper aims to reveal the key molecular markers associated with pyroptosis in IS.

Methods

We used random forest learning, gene set variation analysis, and Pearson correlation analysis to screen for biomarkers associated with pyroptosis in IS. Middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen and glucose deprivation/reoxygenation (OGD/R) models were constructed in vitro and in vivo. Cells were transfected with an Annexin A3 silencing (si-ANXA3) plasmid to observe the effects of ANXA3 on OGD/R + lipopolysaccharides (LPS)-induced pyroptosis. qRT‒PCR and western blotting were used to detect the expression of potential biomarkers and pyroptotic pathways.

Results

Samples from a total of 170 IS patients and 109 healthy individuals were obtained from 5 gene expression omnibus databases. Thirty important genes were analyzed by random forest learning from the differentially expressed genes. Then, we investigated the relationship between the above genes and the pyroptosis score, obtaining three potential biomarkers (ANXA3, ANKRD22, ADM). ANXA3 and ADM were upregulated in the MCAO/R model, and the fold difference in ANXA3 expression was greater. Pyroptosis-related factors (NLRP3, NLRC4, AIM2, GSDMD-N, caspase-8, pro-caspase-1, cleaved caspase-1, IL-1β, and IL-18) were upregulated in the MCAO/R model. Silencing ANXA3 alleviated the expression of pyroptosis-related factors (NLRC4, AIM2, GSDMD-N, caspase-8, pro-caspase-1, cleaved caspase-1, and IL-18) induced by OGD/R + LPS or MCAO/R.

Conclusion

This study identified ANXA3 as a possible pyroptosis-related gene marker in IS through bioinformatics and experiments. ANXA3 could inhibit pyroptosis through the NLRC4/AIM2 axis.
Appendix
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Metadata
Title
Identification of ANXA3 as a biomarker associated with pyroptosis in ischemic stroke
Authors
Linquan Liu
Yahong Cai
Changqing Deng
Publication date
01-12-2023
Publisher
BioMed Central
Keywords
Stroke
Biomarkers
Published in
European Journal of Medical Research / Issue 1/2023
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-023-01564-y

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