FOXN4 Inhibits Breast Cancer Progression By Direct Activation Of P53

BACKGROUND: Fork head domain-containing gene family (Fox) transcription factors, consisting of over 20 members, are involved in the progression of certain types of tumor. However, whether FOXN4 is involved in carcinogenesis and tumor progression is still unclear. PURPOSE: In this study, we investigated the clinicopathological significance and the underlying mechanism of FOXN4 in breast cancer. METHODS AND RESULTS: We examined the lower expression of FOXN4 in breast cancer tissues and cancer cell lines. The expression of FOXN4 is negatively correlated with tumor size and lymph node metastasis. Using CCK-8 assay, colony formation assay, wound healing assay, and Transwell assay, we revealed that FOXN4 notably decreased breast cancer cell proliferation, epithelial-mesenchymal transition and invasion in vitro. In addition, quantitative chromatin immunoprecipitation and luciferase assays determined that FOXN4 was able to directly bind with the promoter of P53. RT-qPCR and Western blotting analysis showed that FOXN4 could directly activate P53 expression. Functionally, P53 knockdown rescued the tumor inhibition effects of FOXN4 in breast cancer cells. CONCLUSION: The present study provides new insights into the role of FOXN4 in breast cancer progression and suggests FOXN4 might represent a potential therapeutic target in breast cancer by modulating P53.