ORIGINAL RESEARCH article
Front. Neurol.
Sec. Stroke
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1633393
This article is part of the Research TopicBrain Cytoprotection for Reperfusion Injury after Acute Ischemic StrokeView all 3 articles
Exosomal circ_0093708 as a Potential Ferroptosis Biomarker in Cerebral Ischemia-Reperfusion Injury
Provisionally accepted
Shuyin MaXiaodong Zhang
Jiaxin FanMengying ChenQingling Yao
Nan ZhangKaili ShiShuang DuYuxuan ChengHuiyang QuMinyu Duan
Han YangTiantian Gao
Shuqin Zhan*- Department of Neurology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Background: Ferroptosis plays a critical role in neuronal injury following cerebral infarction. However, effective therapeutic strategies targeting ferroptosis after cerebral ischemia-reperfusion injury (CI/RI) remain limited. Exosome-based therapy holds significant promise in this context. This study aims to identify key exosomal markers of ferroptosis.Methods: By integrating and analyzing multiple GSE datasets, we identified ferroptosis-associated key genes. These findings were further validated in external databases, cellular models, and animal experiments using malondialdehyde (MDA), glutathione (GSH), iron, reactive oxygen species (ROS) assays, qRT-PCR, Western blotting. By further establishing a ferroptosis model and inhibiting DUSP1 with drugs, we further explored the potential function of DUSP1 in ferroptosis. The role of miR-101-3p was assessed in CI/RI models, while the diagnostic value of exosomal circular RNA was evaluated using receiver operating characteristic curve analysis.Results: Combined differential analysis revealed PTGS2 and DUSP1 as ferroptosisassociated genes potentially regulated by exosomal circRNAs. In cellular and animal models, ferroptosis post-CI/RI was confirmed by elevated MDA, iron, and ROS levels, alongside reduced GSH. DUSP1 expression was significantly upregulated during ferroptosis, as demonstrated by qRT-PCR, Western blotting, and immunofluorescence. In the simple ferroptosis model, the expression of DUSP1 increases and inhibiting DUSP1 can aggravate ferroptosis. Conversely, miR-101-3p was downregulated in CI/RI, consistent with database predictions. Notably, exosomal circ_0093708 exhibited high diagnostic accuracy (Area under the curve = 0.93, sensitivity = 90%, specificity = 90%). Bioinformatics analysis suggested binding interactions among circ_0093708, miR-101-3p, and DUSP1. Conclusion: Exosomal circ_0093708 is linked to DUSP1 and PTGS2 expression by sponging miR-101-3p, positioning it as a potential biomarker for ferroptosis in CI/RI.
Keywords: Exosomes, Cerebral ischemia-reperfusion injury, ferroptosis, DUSP1, circular RNA
Received: 22 May 2025; Accepted: 22 Jul 2025.
Copyright: © 2025 Ma, Zhang, Fan, Chen, Yao, Zhang, Shi, Du, Cheng, Qu, Duan, Yang, Gao and Zhan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shuqin Zhan, Department of Neurology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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