Objective Exploring the dynamic changes of monoamine oxidase A (MAOA) and forkhead box A1 (FOXA1) during neuroendocrine differentiation (NED) in prostate cancer, providing new strategies for the treatment of neuroendocrine prostate cancer (NEPC). Methods Cell models and mouse transplantation models of NED were established through long-term sustained induction of enzalutamide (ENZ); Dynamic expression of MAOA, FOXA1 in NED detected by Western blot and qPCR methods; Selection of GEO database to analyse the dynamic trends of MAOA and FOXA1 in multiple NED models; Construction of mouse transplantation model of human prostate cancer cell lines and analysis of the dynamic expression of MAOA and FOXA1 in NED in the in vivo model by immunohistochemistry; Intervention of MAOA by lentiviral transfection and detection of MAOA's regulation of FOXA1. Results Both MAOA and FOXA1 showed the dynamic characteristics of increasing and then decreasing during NED process; Knockdown of MAOA in prostate cancer cells can lead to decreased expression of FOXA1, which may be the reason why MAOA plays different roles through FOXA1 at different stages of NED.Objective To establish cellular and animal models of neuroendocrine transdifferentiation (NED) in prostate cancer, to further explore the role and mechanism of monoamine oxidase A (MAOA) in the process of NED. Methods The human prostate cancer cell line C4-2 was selected to induce the NED process by long-term stimulation of enzalutamide (ENZ); The changes in the levels of MAOA and Forkhead Box A1 (FOXA1) during the NED process were detected by Real-time PCR and Western blot; and a xenograft model of prostate cancer was established to validate the changes in MAOA and FOXA1 in vivo. The expression of MAOA and FOXA1 was further analyzed by utilizing GEO database sequencing data GSE8702 and GSE59986. Results ENZ can be used as a method to induce NED cellular model and animal model; during the process of ENZ-induced NED, the expression of MAOA and FOXA1 showed a dynamic change character, firstl increasing and then decreasing; Knocking down MAOA expression in prostate cancer can lead to the decrease of FOXA1 expression, which may be the various roles of MAOA through regulation of FOXA1 at different stages of NED. Conclusions Both MAOA and FOXA1 showed a trend of increasing and then decreasing during NED, and the expression of MAOA could affect the level of FOXA1, and MAOA/FOXA1 may play a dynamic regulatory role in the NED process.