Circular RNA HIPK3 mediates epithelial–mesenchymal transition of retinal pigment epithelial cells by sponging multiple microRNAs

• Published in: Scientific reports 2024-11, Vol.14 (1), p.28872-10, Article 28872
• Main Authors: Feng, Yalan, Yang, Fan, Zheng, Jijia, Shi, Lijun, Xie, Tianhua, Lin, Yunzhi, Shi, Qian
• Format: Article
• Language: English
• Subjects: 631/337/384/331; 631/80/84/2176; Antibodies; Cell Line; circHIPK3; Circular RNA; Competing endogenous RNA; Epithelial Cells - metabolism; Epithelial-Mesenchymal Transition - genetics; Epithelial–mesenchymal transition; Gene expression; Gene Expression Regulation; Hospitals; Humanities and Social Sciences; Humans; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Laboratory animals; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; multidisciplinary; Ophthalmology; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Proteins; Retina; Retinal pigment epithelium; Retinal Pigment Epithelium - cytology; Retinal Pigment Epithelium - metabolism; RNA - genetics; RNA - metabolism; RNA, Circular - genetics; RNA, Circular - metabolism; Science; Science (multidisciplinary); Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b1
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-71119-6

Epithelial–mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells plays key roles in the pathogenesis of multiple vitreoretinal diseases, leading to profound and permanent vision loss. Circular RNAs (circRNAs) are widespread and functional endogenous RNAs that could regulate gene expression in eukaryotes. The functions of circRNAs in mediating EMT has been reported in several diseases. In the current study, we investigated the role of circRNA HIPK3 (circHIPK3) in EMT process of RPE cells (RPE-EMT). circHIPK3 is one abundant circRNA generated from the second exon of HIPK3 mRNA. We found that circHIPK3 expression was significantly increased in TGF-β1-induced RPE-EMT model. Silencing of circHIPK3 attenuated TGF-β1-induced RPE-EMT process, whereas forced expression of circHIPK3 could trigger EMT in RPE cells. Mechanistically, circHIPK3 regulates RPE-EMT process via sponging multiple microRNAs (miRNAs). This study provides novel insights into the mechanism of RPE-EMT. Targeting circHIPK3 might serve as a therapeutic strategy in RPE-EMT associated vitreoretinal diseases.