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. The gene discussed is CCND1; the disease is cancer.