RNF112 mediates immunosuppression to inhibit the proliferation of cervical cancer by Foxm1.

Background: Cervical cancer ranks as the fourth most common malignant tumor among women worldwide. However, the molecular mechanisms driving tumor progression and immune evasion in this disease have not been sufficiently clarified. The aim of this study was to determine the expression profile and clinical significance of ring finger protein 112 (RNF112) in cervical cancer and to elucidate the molecular mechanism by which RNF112 regulates tumor proliferation and immune response. Methods: The expression of RNF112 in tumor tissues from patients with cervical cancer and from healthy controls was analyzed via quantitative polymerase chain reaction and Western blotting. The correlation between RNF112 expression and survival of patients with cervical cancer was analyzed. The human immortalized cervical epithelial cell line (H8) and cervical cancer cell lines were used for Results: RNF112 expression was significantly downregulated in both cervical cancer patient tissues and cell lines as compared to that from samples of healthy controls. Clinical analysis revealed that low RNF112 expression was associated with poor prognosis. In the mouse model, sh-RNF112 significantly promoted tumor growth. In terms of mechanism, RNF112 was found to alleviate the immunosuppressive state within the tumor microenvironment (TME). Specifically, RNF112 reduced oxidative stress, mitigated mitochondrial dysfunction, and suppressed ferroptosis in T lymphocytes. Furthermore, RNF112 promoted the ubiquitination and degradation of Foxm1; conversely, inhibition of Foxm1 reversed the tumor-promoting effects induced by RNF112 knockdown. Conclusions: RNF112 functions as a tumor suppressor in cervical cancer. By promoting Foxm1 ubiquitination, RNF112 inhibits tumor proliferation and alleviates immunosuppression, thereby protecting against oxidative stress-induced mitochondrial dysfunction and ferroptosis in T lymphocytes.