Identification of UPB1 as a tumor suppressor associated with immune infiltration in cholangiocarcinoma

Background: Cholangiocarcinoma (CCA) remains one of the most aggressive malignancies within the digestive tract, and identifying novel biomarkers and therapeutic targets is essential to improve patient survival. Recent studies have highlighted Beta-Ureidopropionase 1 (UPB1) as a predictive biomarker across multiple tumor types, but its biological involvement in CCA development and progression remains unclear.Methods: A combination of bioinformatics analyses and clinical data evaluation was applied to investigate UPB1 expression in CCA. Functional assays in cell models and xenograft mouse experiments were carried out to assess the influence of UPB1 on CCA growth. Co-culture assays were utilized to examine how UPB1 expression influences tumor immune infiltration.Results: Reduced UPB1 expression in CCA was correlated with unfavorable clinical manifestations and poor survival outcomes. In vitro studies demonstrated that UPB1 promoted apoptosis through the regulation of BCL-2 and BIRC5 and induced G1/S cell cycle arrest via the CDK2/CCNA2 pathway. In vivo experiments further confirmed the tumor-suppressive function of UPB1. Moreover, UPB1 expression showed a positive correlation with tumor-infiltrating lymphocytes, and UPB1 overexpression upregulated T-cell activation–related transcripts and increased the release of immune factors.Conclusion: UPB1 functions as a tumor suppressor in CCA and is associated with enhanced tumor immune infiltration. These results deepen the understanding of CCA biology and highlight UPB1 as a promising therapeutic candidate.