Tumor necrosis factor-α-induced protein 8 (TNFAIP8) is a member of TIPE/TNFAIP8 family, has been involved in the development and progression of various human cancers. We hypothesized that TNFAIP8 promotes prostate cancer (PCa) progression via regulation of oxidative phosphorylation (OXPHOS) and glycolysis. Ectopic expression of TNFAIP8 increased PCa cell proliferation/migration/spheroid formation by enhancing cell metabolic activities. Mechanistically, TNFAIP8 activated the PI3K-AKT pathway and up-regulated PCa cell survival. TNFAIP8 was also found to regulate the expression of glucose metabolizing enzymes, enhancing glucose consumption, and endogenous ATP production. Treatment with a glycolysis inhibitor, 2-deoxyglucose (2-DG), reduced TNFAIP8 mediated glucose consumption, ATP production, spheroid formation, and PCa cell migration. By maintaining mitochondrial membrane potential, TNFAIP8 increased OXPHOS and glycolysis. Moreover, TNFAIP8 modulates the production of glycolytic metabolites in PCa cells. Collectively, our data suggest that TNFAIP8 exerts its oncogenic effects by enhancing glucose metabolism and by facilitating metabolic reprogramming in PCa cells. Therefore, TNFAIP8 may be a biomarker associated with prostate cancer and indicate a potential therapeutic target.

肿瘤坏死因子-α诱导蛋白8（TNFAIP8）是TIPE/TNFAIP8家族的成员，已参与多种人类癌症的发生和进展。我们假设 TNFAIP8 通过调节氧化磷酸化 (OXPHOS) 和糖酵解来促进前列腺癌 (PCa) 进展。 TNFAIP8 的异位表达通过增强细胞代谢活动来增加 PCa 细胞增殖/迁移/球体形成。从机制上讲，TNFAIP8 激活 PI3K-AKT 通路并上调 PCa 细胞存活。 TNFAIP8 还被发现可以调节葡萄糖代谢酶的表达，增强葡萄糖消耗和内源 ATP 产生。用糖酵解抑制剂 2-脱氧葡萄糖 (2-DG) 治疗，可减少 TNFAIP8 介导的葡萄糖消耗、ATP 产生、球状体形成和 PCa 细胞迁移。通过维持线粒体膜电位，TNFAIP8 增加 OXPHOS 和糖酵解。此外，TNFAIP8 调节 PCa 细胞中糖酵解代谢物的产生。总的来说，我们的数据表明 TNFAIP8 通过增强葡萄糖代谢和促进 PCa 细胞中的代谢重编程来发挥其致癌作用。因此，TNFAIP8可能是与前列腺癌相关的生物标志物并表明潜在的治疗靶点。