USP22 and cancer: Moreover, DNA- and RNA-sequencing data show that the genes encoding histone E3 ubiquitin ligases and DUBs are also frequently altered in cancers [91], and many of the enzymes possess tumor suppressor (e.g., BAP1 and RNF20) or oncogenic potential (e.g., BMI1 and USP22) [44,70,92,93,94], identifying possible mechanism(s) accounting for the aberrant histone ubiquitination levels observed within those cancers.