Thus, USP22 upregulation has widely been proposed to support oncogenic-driven proliferation of cancer cells by increasing the abundance of oncogenic transcription factors and the expression of their target genes [10,67,69]; however, it should be noted that the role of USP22 as transcriptional activator is not limited to the expression of oncogene targets, as USP22 is also required for active transcription of multiple target genes of TP53, a major tumor suppressor [8]. This evidence concerns the gene USP22 and cancer.