Taken together, this study revealed that a hypoxia-responsive circRNA, circAAGAB, interacted with FUS to avoid degradation, sponged miR-378 h to up-regulate KIAA1522, NKX3-1, and JADE3, restrained cell colony formation, cell migration and invasion, and increased radiosensitivity in breast cancer cells through the p38 MAPK signaling pathway. This evidence concerns the gene NHSL3 and breast cancer.