The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity

Abstract

Abstract 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 in vitro model. Foxp1 increased the Warburg effect of bladder cancer. Foxp1 suppressed β-adrenoceptor (β-AR) expression in vitro 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 in vitro model. β-AR reduced the effects of Foxp1 on the Warburg effect in vitro 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.