USP22 and cancer: USP22 catalyzes the removal of the mono-ubiquitin moiety from H2Bub1 and other critical tumor-associated proteins such as c-Myc [17, 48], SIRT1 [34], CCNB1/D1 [54, 55], androgen receptor (AR) [36], BMI1 [36], and FBP1 [56], and has been proven to play multiple and critical roles in cancer growth, stemness, DNA damage response (DDR) [30], resistance to chemotherapy.