CircRNF10 sequestrates β-catenin by a dual regulatory circuit of direct degradation and a miR-1275/DKK3-mediated inhibition in driver gene- negative lung adenocarcinoma

作者：Xiaohua Situ, Xin Wei Wang, Xiting Liao, Xiaoxuan Zhang, Sicheng Chen, Fei Fang, Lihong Wei, Peng Wu, Zhiyu Liu, Honglei Chen, Kejing Tang, Lihong Bai, Zunfu Ke · 发表于：Molecular Cancer · 年份：2025 · DOI：10.1186/s12943-025-02530-4 · 研究领域：Circular RNAs in diseases、Ferroptosis and cancer prognosis、Cancer Mechanisms and Therapy

BACKGROUND: Circular RNAs (circRNAs) exert critical regulatory functions in tumor biology by modulating pathways associated with oncogenesis or tumor suppression. Despite substantial progress in elucidating their roles in several malignancies, the contribution of circRNAs to the pathogenesis of driver gene-negative lung adenocarcinoma (LUAD), a molecular subtype lacking actionable genetic alterations and exhibiting limited response to existing targeted or immunotherapeutic strategies, remains poorly defined. METHODS: The expression of circRNF10 in driver gene-negative LUAD was analyzed using circRNA microarray analysis followed by RT-qPCR validation. A series of functional assays were performed both in vitro and in vivo to evaluate the effects of circRNF10 on tumor cell behavior, including proliferation (EdU incorporation), migration (wound healing), and invasion (transwell assays), as well as tumor growth in a murine model. To elucidate the underlying molecular mechanism, we employed a combination of computational and experimental approaches, including AlphaFold3-based structural prediction, in vitro transcription, biotin-labeled RNA pulldown, RNA immunoprecipitation (RIP), and dual-luciferase reporter assays. RESULTS: In this study, we identified a previously uncharacterized circular RNA, circRNF10, which is markedly downregulated in driver gene-negative lung adenocarcinoma (LUAD) and positively associated with favorable clinical outcomes. Functional analyses revealed that ...