To investigate the significance of DCUN1D5 in colorectal cancer (CRC) progression and determine the underlying mechanism.

We analyzed DCUN1D5 expression levels in CRC tissues using the TCGA and GEO databases and conducted immunohistochemistry and qPCR in retrieved CRC tissues. shRNA-mediated knockdown of DCUN1D5 in CRC cell lines was performed to investigate its effects on cell growth and motility. In addition, DCUN1D5-mediated promotion of CUL1 neddylation was examined using immunoblotting, the antitumor effects of inhibiting the neddylation pathway was evaluated using the inhibitor MLN4924, and the effects of silencing DCUN1D5 and MLN4924 treatment were validated in vivo using xenograft models.

DCUN1D5 was found to be significantly overexpressed in CRC tissues, and its knockdown impaired CRC cell proliferation and migration, which was associated with reduced CUL1 neddylation. Inhibition of the neddylation pathway using the NEDD8 inhibitor MLN4924 supported these observations. In vivo, DCUN1D5 silencing and MLN4924 treatment led to reduced tumor growth and metastasis.

DCUN1D5 contributes to the growth and motility of CRC in vitro and in vivo.