CircAbcc1-encoded ABCC1-677aa modulates DLX1 to suppress ferroptosis in chronic cerebral ischemiaDownload PDF Download PDF ArticleOpen accessPublished: 14 October 2026Jiashuo Yang ORCID: orcid.org/0009-0001-2490-14151 na1,Yan Yu2 na1,Jinlin Fan1,Kunlong Hong1,Naibo Zhang1 &…Jian Zheng ORCID: orcid.org/0009-0007-7069-80871 Communications Biology (2026) Cite this articleView saved research We’re sharing this article early to provide faster access to peer-reviewed, accepted research. It is citable and carries a permanent DOI. This version is subject to further edits and will be replaced automatically by the final Version of Record. All legal disclaimers apply.AbstractCerebral ischemia leads to progressive neurological dysfunction due to restricted blood perfusion in the brain. While circular RNAs are known to regulate pathological processes, their ability to encode functional proteins during ischemic injury remains unclear. Here, we show that the circular RNA circAbcc1 suppresses ferroptosis in mouse and cellular models of chronic cerebral ischemia‘. We found that circAbcc1 translates into a functional protein, ABCC1-677aa. This protein actively interacts with and phosphorylates the transcription factor DLX1, triggering its export from the nucleus to the cytoplasm. This translocation prevents DLX1 from transcriptionally repressing the crucial anti-ferroptotic genes, Gpx4 and Fsp1. The subsequent upregulation of Gpx4 and Fsp1 limits lipid peroxidation and iron accumulation, successfully protecting brain neurons from ferroptosis. These findings elucidate a regulatory mechanism driven by a circular RNA-encoded protein and identify the circAbcc1-DLX1 axis as a potential therapeutic target for cerebral ischemic injury.AcknowledgementsNot applicable.FundingThis work is supported by the Education Department of Liaoning Provincial Basic Research Projects (JYTMS20230098) and the 30 Project Fund of Shengjing Hospital (M0269).Author informationAuthor notesThese authors contributed equally: Jiashuo Yang, Yan Yu.Authors and AffiliationsDepartment of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, ChinaJiashuo Yang, Jinlin Fan, Kunlong Hong, Naibo Zhang & Jian ZhengDepartment of Radiology, Shengjing Hospital of China Medical University, Shenyang, ChinaYan YuAuthorsJiashuo YangView author publicationsSearch author on:PubMed Google ScholarYan YuView author publicationsSearch author on:PubMed Google ScholarJinlin FanView author publicationsSearch author on:PubMed Google ScholarKunlong HongView author publicationsSearch author on:PubMed Google ScholarNaibo ZhangView author publicationsSearch author on:PubMed Google ScholarJian ZhengView author publicationsSearch author on:PubMed Google ScholarCorresponding authorCorrespondence to Jian Zheng.Ethics declarationsCompeting interestsThe authors declare no competing interests.Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary informationRights and permissionsOpen Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.Reprints and permissionsAbout this article