Ding Zhenshan, Jiao Binbin, Chen Xuelong, Chen Xing, Jiao Yangtian, Wang Jianfeng, Zhou Xiaofeng
Department of Urology, China-Japan Friendship Hospital, No. 2, Yinghua East Road, Chaoyang District, Beijing 100029, China.
Department of Urology, China-Japan Friendship Hospital, Beijing 100029, China.
Open Med (Wars). 2023 Aug 24;18(1):20230647. doi: 10.1515/med-2023-0647. eCollection 2023.
Bladder cancer is a common malignant tumor. FOXP1 has been found to be abnormally expressed in tumors such as renal cell carcinoma and endometrial cancer. Here, this investigated the biological roles of Foxp1 in the occurrence and development of bladder cancer. Patients with bladder cancer were obtained from China-Japan Friendship Hospital. Bladder cancer cell lines (5637, UMUC3, J82, and T24 cell) were used in this experiment. Foxp1 mRNA and protein expression levels in patients with bladder cancer were increased, compared with paracancerous tissue (normal). OS and DFS of Foxp1 low expression in patients with bladder cancer were higher than those of Foxp1 high expression. Foxp1 promoted bladder cancer cell growth model. Foxp1 increased the Warburg effect of bladder cancer. Foxp1 suppressed β-adrenoceptor (β-AR) expression model. ChIP-seq showed that Foxp1 binding site (E1, TTATTTAT) was detected at -2,251 bp upstream of the β-AR promoter. β-AR Reduced the effects of Foxp1 on cell growth model. β-AR reduced the effects of Foxp1 on the Warburg effect model by STAT3 activity. Taken together, our findings reveal that Foxp1 promoted the occurrence and development of bladder cancer through the Warburg effect by the activation of STAT3 activity and repressing β-AR transcription, and which might serve as an important clue for its targeting and treatment of bladder cancer.
膀胱癌是一种常见的恶性肿瘤。已发现FOXP1在肾细胞癌和子宫内膜癌等肿瘤中异常表达。在此，本研究探讨了Foxp1在膀胱癌发生发展中的生物学作用。膀胱癌患者来自中日友好医院。本实验使用了膀胱癌细胞系（5637、UMUC3、J82和T24细胞）。与癌旁组织（正常组织）相比，膀胱癌患者中Foxp1 mRNA和蛋白表达水平升高。膀胱癌患者中Foxp1低表达的总生存期（OS）和无病生存期（DFS）高于Foxp1高表达者。Foxp1促进膀胱癌细胞生长模型。Foxp1增强了膀胱癌的瓦博格效应。Foxp1抑制β-肾上腺素能受体（β-AR）表达模型。染色质免疫沉淀测序（ChIP-seq）显示，在β-AR启动子上游-2251 bp处检测到Foxp1结合位点（E1，TTATTTAT）。β-AR降低了Foxp1对细胞生长模型的影响。β-AR通过信号转导和转录激活因子3（STAT3）活性降低了Foxp1对瓦博格效应模型的影响。综上所述，我们的研究结果表明，Foxp1通过激活STAT3活性和抑制β-AR转录，通过瓦博格效应促进膀胱癌的发生发展，这可能为其靶向治疗膀胱癌提供重要线索。
