To elucidate how UBE2M promotes CRC progression, we conducted in vivo and in vitro experiments to confirm the role of UBE2M in neddylating USP39, which in turn modulates the deubiquitination of PABPC1, enhances the translation efficiency of CCNB1 and propels the cell cycle progression of CRC. This evidence concerns the gene CCNB1 and colorectal carcinoma.