ADARB1 inhibits glycolysis and progression of cervical cancer through the HMGB1/PFKFB3 axis

Cervical cancer (CC) remains one of the most prevalent gynecological malignancies worldwide, with patients diagnosed at advanced stages often facing poor prognoses due to the lack of effective therapeutic options. ADARB1 (Adenosine Deaminase Acting on RNA 1), an RNA-editing enzyme, has been implicated in the pathogenesis of various cancers; however, its functional role in cervical cancer remains largely unexplored. In this study, we observed a significant downregulation of ADARB1 expression in both cervical cancer tissues and cell lines, which was associated with unfavorable clinical outcomes. Functional assays revealed that ADARB1 overexpression markedly inhibited the proliferation, migration, invasion, and glycolytic activity of cervical cancer cells, whereas ADARB1 knockdown exerted the opposite effects. Mechanistically, we found that ADARB1 mRNA binds to HMGB1 (High Mobility Group Box 1) protein and regulates its expression via the ubiquitin-proteasome pathway, thereby modulating the malignant phenotype of cervical cancer. Notably, ectopic expression of HMGB1 partially reversed the suppressive effects of ADARB1 on cell proliferation and glycolysis. Further investigation revealed that HMGB1 interacts with PFKFB3 (6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase 3), a key regulatory enzyme in glycolysis, and modulates its protein stability, suggesting the presence of a critical HMGB1/PFKFB3 signaling axis in cancer metabolism. ADARB1 exerts its anti-tumor effects primarily through the HMGB1/PFKFB3 pathway. Collectively, these findings identify ADARB1 as a novel tumor suppressor in cervical cancer and a promising therapeutic target for clinical intervention.