Forkhead Box F1 acts as a novel prognostic biomarker and induces caspase-dependent apoptosis in bladder cancer
Down-regulated expression of Forkhead Box F1 (FOXF1) in malignant tumors were reported in several kinds of cancer before, but its role in bladder cancer (BC) was not clear. This study aims to demonstrate the prognostic value and of FOXF1 in BC patients. Here, a retrospectively recruited BC cohort and public datasets were utilized to identify the predictive ability of FOXF1 and its relationship between clinical information in BC patients. The expression level of FOXF1 is notably higher in BC tissues than para-cancerous mucosae. Low FOXF1 expression is correlated to unfavorable clinicopathological features and poor prognosis. Further, in bladder tumor cells, the expression levels of FOXF1 mRNA and protein were tested by quantitative real-time PCR and western blot. The viability of cells was examined by CCK-8, EdU, and clonogenic capacity assays. Cell apoptosis was detected by flow cytometry. We note that FOXF1 activating could impair cell viability and induce apoptosis in BC. Then, caspase 3 as a downstream gene of FOXF1 was spotted by RNA-Seq and PPI. The anti-tumor effect of FOXF1 were also validated in animal models. In conclusion, down-regulated FOXF1 expression is a potential independent indicator for unfavorable clinical outcomes of BC patients, FOXF1 inhibits BC cells proliferation and induces cell apoptosis via caspase signaling pathway. This study exhibits FOXF1 express pattern, demonstrates the prognostic predictive ability of FOXF1 and prove the anti-tumor mechanisms of FOXF1 in BC, it has reference value to clinical decision, activation FOXF1 expression could be used as a new strategy in tumor therapeutics. Overall design: human bladder cancer cell line T24, FOXF1-activated and negative control, 3 replicates per group