Circular RNAs (circRNAs) are stable noncoding RNAs involved in cancer, yet their mechanisms in lung adenocarcinoma (LUAD) remain unclear. This study explores the oncogenic role of circUBAC2 in LUAD progression. Differentially expressed circRNAs were screened by microarray. circUBAC2 expression/location was analyzed via quantitative real-time PCR (qRT-PCR), RNA in situ hybridization (RNA-ISH), and fluorescence in situ hybridization. Functional impacts were evaluated through wound healing, Transwell, EdU, colony formation, and xenograft models. circUBAC2 targets were identified by RNA-sequencing/proteomics, with protein interactions assessed via western blotting, immunoprecipitation, and ubiquitination assays. Molecular interactions were examined using dual luciferase, chromatin Immunoprecipitation (ChIP), and RNA pull-down. circUBAC2 was upregulated in LUAD tissues and correlated with poor prognosis. It promoted LUAD cell proliferation, migration, and invasion in vitro, as well as tumor growth/metastasis in vivo. Mechanistically, circUBAC2 competitively bound 14-3-3 to release YAP for nuclear translocation while scaffolding OTUB1–YAP interactions to enhance YAP deubiquitination and stabilization, collectively activating TEAD-mediated oncogenic transcription. EIF4A3 facilitated circUBAC2 biogenesis by binding flanking intronic regions. circUBAC2 drives LUAD progression via YAP signaling, positioning it as a therapeutic target and prognostic biomarker.
Meng et al. (Sun,) studied this question.