RRM2 and breast cancer: FBXO1 was negatively regulated by the E3 ligase (FZR1) and the co-regulator of E3 ligase (FBXL8), which were known to play an oncogenic role in breast cancer, and FBXO1 could inhibit the expression of ribonucleotide reductase M2 (RRM2), a pro-tumorigenic protein (35).