A novel circular RNA hsa_circ_0079474 facilitates intrauterine adhesion by targeting miR-630/YAP1 axis to stimulate epithelial-mesenchymal transition.

Emerging evidence highlights the critical role of circular RNAs (circRNAs) in regulating pathological processes in various diseases, including organ fibrosis. Endometrial fibrosis, commonly referred to as intrauterine adhesion (IUA), is a major cause of uterine infertility. However, the involvement of circRNAs in the pathogenesis of IUA remains largely unexplored, necessitating further research. This study aimed to identify a specific circRNA that may serve as a diagnostic biomarker and therapeutic target for IUA. CircRNA microarray analysis was performed to compare circRNA expression profiles between paired fibrotic and normal endometrial samples from patients with IUA. The expression of hsa_circ_0079474 was significantly upregulated in fibrotic tissues compared with normal tissues. Functional analyses demonstrated that hsa_circ_0079474 enhanced cell proliferation, promoted cell cycle progression, and facilitated epithelial-mesenchymal transition (EMT) in vitro, as assessed by qRT-PCR, CCK-8 assays, EdU assays, flow cytometry, and Masson staining. Mechanistically, dual-luciferase reporter assays and RNA immunoprecipitation confirmed that hsa_circ_0079474 acted as a molecular sponge for miR-630, leading to the upregulation of YAP1. In an IUA rat model, hsa_circ_0079474 was found to drive EMT, whereas miR-630 administration reversed this process and ameliorated endometrial fibrosis. Consequently, these findings indicate that hsa_circ_0079474 contributes to the progression of IUA by modulating the miR-630/YAP1 axis, providing new insights into circRNA-mediated mechanisms in IUA and highlighting hsa_circ_0079474 as a potential therapeutic target.