RNF125 promotes CD8 T cell-mediated anticancer immunity and suppresses the malignant phenotype of cervical cancer

Cervical cancer (CC) is a prevalent malignancy in women; however, the efficacy of immunotherapy in this disease is suboptimal, highlighting the need for novel therapeutic targets. We found that low RNF125 expression correlated with poor prognosis in CC patients. In vitro and in vivo, RNF125 inhibited proliferation and induced apoptosis of CC cells. In immunocompetent mice, RNF125 suppressed tumor growth, increased CD8⁺ T cell infiltration, elevated IFN-γ secretion, and reduced PD-1 expression on CD8⁺ T cells. Co-culture experiments confirmed that tumor cells overexpressing RNF125 enhanced CD8⁺ T cell proliferation and function. Further mechanistic investigation revealed that RNF125 promoted CD8⁺ T cell activity by ubiquitinating and degrading PD-L1. Additionally, RNF125 was identified as a direct target of miR-574-5p. This study demonstrates that RNF125 exhibits tumor-suppressive functions in CC by enhancing anti-tumor immunity, highlighting its therapeutic potential.