By using RNAseq and Go ocology enrichment analysis, we found that USP22 knockout had pronounced effects on the expression of these important cancer-associated genes including ALDH1A3, CCND1/2, CCNG1, Set7/9, c-Myc etc., significantly suppressed angiogenesis, cell cycle progression, EMT, RAS, c-Myc signaling pathways; and concurrently enhanced oxidative phosphorylation and tight junction signaling pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) in the two cells. This evidence concerns the gene SETD7 and cancer.