KDM5B recruits FOXG1 to suppress the IFN response, leading to malignant progression and immune evasion in cervical cancer

Introduction Cervical cancer carcinogenesis often exhibits significant heterogeneity, and the molecular mechanisms underlying epithelial cell transformation are not fully understood. Methods Single-cell RNA sequencing was employed to compare the immune microenvironment of normal cervix and cervical cancer. Immunohistochemistry was applied to measure the expression of KDM5B in patient samples. qPCR and western blot were performed to detect the KDM5B expression and activation of IFN pathway in cell line. Co-immunoprecipitation (COIP), immunofluorescence (IF) and surface plasmon resonance (SPR) are employed to detect the binding between KDM5B and FOXG1. Flow cytometry was conducted to evaluate the immune infiltration of mice tumor. Results This study reveals that malignant progression in cervical cancer is characterized by substantial DNA damage and marked upregulation of the histone demethylase KDM5B. We also identified a novel regulatory mechanism by which KDM5B recruits the transcriptional repressor FOXG1 to suppress the interferon signaling pathway, thereby promoting malignant behaviors and immune escape in cervical cancer. Targeting KDM5B could effectively enhance anti-tumor immunity. Discussion These findings provide crucial insights into the biological role of KDM5B in cervical cancer and highlight its potential as a promising therapeutic target for immunotherapy.