Trim45 promotes the occurrence and development of cervical cancer by inhibiting the cGAS/STING signaling pathway.

Cervical cancer is a gynecological malignancy closely associated with high-risk human papillomavirus infection. Trim45, a member of the E3 ubiquitin ligase family, is highly expressed in cervical cancer tissues; however, its specific mechanistic contribution to disease progression remains incompletely understood. By integrating single-cell sequencing, functional assays, and molecular profiling, we found that single-cell sequencing and IHC analyses revealed high Trim45 expression in cervical cancer tissues from patients with HPV-18 infection. Furthermore, we uncovered a novel mechanism by which Trim45 promotes cervical cancer progression: Trim45 suppresses the cGAS/STING signaling pathway activity by mediating ANXA2, which subsequently upregulates the expression of the key glycolytic enzymes HK2 and ENO2, enhances the aerobic glycolysis capacity of tumor cells, and ultimately promotes cervical cancer proliferation and metastasis. Collectively, these findings elucidate the molecular mechanism by which Trim45 drives the malignant progression of cervical cancer through the "ANXA2-cGAS/STING-glycolysis" axis. Statement of Integration, Innovation and Insight This study integrates single-cell sequencing and functional assays to reveal that Trim45, highly expressed in HPV-18 positive cervical cancer, suppresses the cGAS/STING innate immune signaling pathway by mediating ANXA2. This suppression subsequently upregulates the key glycolytic enzymes HK2 and ENO2, thereby enhancing aerobic glycolysis in tumor cells, and promotes proliferation and metastasis. These findings uncover a novel Trim45-ANXA2-cGAS/STING-glycolysis axis, offering potential therapeutic co-targets.