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journal article·2025-07Open access

Collaborative Duality of CircGLIS3(2) RNA and Protein in human Wound Repair

Guanglin Niu, Maria A. Toma, Jennifer Geara, Xiaowei Bian, Yongjian Chen, Lihua Luo, Qizhang Wang, Yunting Xiao, Manika Vij, Minna Piipponen, Zhuang Liu, Sho Oasa, Letian Zhang, Dörte Schlesinger, Ákos Végvári, Dongqing Li, Aoxue Wang, Vladana Vukojević, Simon J Elsässer, Pehr Sommar, Ning Xu Landén

Advanced Science· Volume 12· Issue 25
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Source abstract

Abstract

Abstract The discovery of an increasing number of translatable circular RNAs (circRNAs) raises the question of whether their coding and non‐coding functions can coexist within the same cell. This study profiles the dynamic expression of circRNAs during human skin wound healing. CircGLIS3(2) is identified, a circRNA whose levels transiently rise in dermal fibroblasts of acute wounds and are abnormally overexpressed in keloids, a fibrotic skin condition. Injury signals such as IL‐1α, TGF‐β, hypoxia, and ER stress induce both expression and cap‐independent translation of CircGLIS3(2). The RNA form of CircGLIS3(2) activates fibroblasts into matrix‐secreting cells, while its encoded protein promotes cell proliferation, collectively enhancing wound repair. Mechanistically, CircGLIS3(2) RNA stabilizes the cytoplasmic protein PCOLCE, while its protein binds to BTF3 in the nucleus. Both the RNA and protein are essential for wound closure in human and murine models. CircGLIS3(2) ’s bifunctional nature expands its functional spectrum, improving cellular adaptability during environmental changes and offering a promising therapeutic target for wound repair and scar reduction.
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Research context

OpenAlex topics: Circular RNAs in diseases · Cancer-related molecular mechanisms research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Dermatology and Venereology Division Department of Medicine Solna Center for Molecular Medicine Karolinska Institutet Stockholm 17176 Sweden

Department of Oromaxillofacial Head and Neck Oncology Shanghai Ninth People's Hospital College of Stomatology Shanghai Jiao Tong University School of Medicine Shanghai 200025 China

Key Laboratory of Basic and Translational Research on Immune‐Mediated Skin Diseases Chinese Academy of Medical Sciences Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing 210003 China

Department of Clinical Neuroscience Center for Molecular Medicine Karolinska Institutet Stockholm 17176 Sweden

Science for Life Laboratory Department of Medical Biochemistry and Biophysics Division of Genome Biology Karolinska Institutet Stockholm 17165 Sweden

Division of Chemistry I Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm 17177 Sweden

Department of Dermatology The Second Hospital of Dalian Medical University College of Integrative Medicine Dalian Medical University Dalian 116021 China

Department of Plastic and Reconstructive Surgery Karolinska University Hospital Stockholm 17176 Sweden

Funding

Stiftelsen Syskonen Svenssons Stiftelse för Medicinsk Forskning · Åke Wiberg Stiftelse · Cancerfonden · LEO Fondet · Ragnar Söderbergs stiftelse · Vetenskapsrådet

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