Circular RNA circASH1L(4,5) protects microRNA-129-5p from target-directed microRNA degradation in human skin wound healing

作者：Qizhang Wang, Guanglin Niu, Zhuang Liu, Maria A. Toma, Jennifer Geara, Xiaowei Bian, Letian Zhang, Minna Piipponen, Dongqing Li, Aoxue Wang, Pehr Sommar, Ning Xu · 发表于：British Journal of Dermatology · 年份：2024 · DOI：10.1093/bjd/ljae405 · 被引用次数：11 · 研究领域：Circular RNAs in diseases、MicroRNA in disease regulation、Connective Tissue Growth Factor Research

BACKGROUND: Skin wound healing involves a complex gene expression programme that remains largely undiscovered in humans. Circular RNAs (circRNAs) and microRNAs (miRNAs) are key players in this process. OBJECTIVES: To understand the functions and potential interactions of circRNAs and miRNAs in human skin wound healing. METHODS: CircRNA, linear RNA and miRNA expression in human acute and chronic wounds were analysed with RNA sequencing and quantitative reverse transcription polymerase chain reaction. The roles of circASH1L(4,5) and miR-129-5p were studied in human primary keratinocytes (proliferation and migration assays, microarray analysis) and ex vivo wound models (histological analysis). The interaction between circASH1L(4,5) and miR-129-5p was examined using luciferase reporter and RNA pulldown assays. RESULTS: We identified circASH1L(4,5) and its interaction with miR-129-5p, both of which increased during human skin wound healing. Unlike typical miRNA sponging, circASH1L enhanced miR-129 stability and silencing activity by protecting it from target-directed degradation triggered by NR6A1 mRNA. Transforming growth factor-β signalling - crucial in wound healing - promoted circASH1L expression while suppressing NR6A1, thereby increasing the abundance of miR-129 at the post-transcriptional level. CircASH1L and miR-129 enhanced keratinocyte migration and proliferation, crucial processes for the re-epithelialization of human wounds. CONCLUSIONS: Our study uncovered a novel rol...