circCOL3A1 Facilitates Esophageal Squamous Cell Carcinoma Progression by Stabilizing YBX1 through Enhanced USP10-Mediated Deubiquitination

Background Recent findings suggest that circular RNAs (circRNAs) play important roles in tumor growth and cancer advancement. However, the specific biological functions and mechanisms of circRNAs in esophageal squamous cell carcinoma remain largely unclear. Methods To identify differentially expressed circular RNAs (circRNAs), we analyzed GEO circRNA microarray datasets. circCOL3A1 expression was validated in ESCC cell lines and a clinical cohort comprising 100 paired tissue samples using quantitative reverse transcription PCR (qRT-PCR). The circular nature of circCOL3A1 was confirmed through RNase R digestion assays and divergent primer-based PCR amplification. Functional investigations, including in vitro and in vivo experiments, were performed to assess the role of circCOL3A1 in cellular proliferation, migration, and invasion. Mechanistic studies were conducted using Western blot analysis, RNA immunoprecipitation (RIP), co-immunoprecipitation (Co-IP), and ubiquitination assays to elucidate the molecular pathways involving circCOL3A1. Results CircCOL3A1 expression was markedly elevated in both ESCC tissues and cell lines, exhibiting a significant association with advanced TNM stages and reduced overall survival. Functionally, circCOL3A1 facilitated ESCC cell proliferation, migration, and invasion in vitro, while also promoting tumor growth in vivo. Mechanistic investigations demonstrated that circCOL3A1 directly bound to the transcription factor YBX1, acting as a protein scaffold to strengthen its interaction with the deubiquitinase USP10. Consequently, this interaction enhanced YBX1 deubiquitination, increased its protein stability, and led to YBX1 accumulation, thereby accelerating ESCC progression. Rescue experiments further validated YBX1 as a pivotal downstream mediator of circCOL3A1. Conclusion Our study elucidates that circCOL3A1 exacerbates ESCC malignancy by stabilizing YBX1 via USP10-mediated deubiquitination. These findings suggest that circCOL3A1 could serve as both a prognostic biomarker and a therapeutic target in ESCC.