Vitamin D3 Upregulated Protein 1 Deficiency Promotes Azoxymethane/Dextran Sulfate Sodium-Induced Colorectal Carcinogenesis in Mice

VDUP1 acts as a tumor suppressor gene in various cancers. VDUP1 is expressed at low levels in sporadic and ulcerative-colitis-associated colorectal cancer. However, the effects of <i>VDUP1</i> deficiency on CAC remain unclear. In this study, we found that <i>VDUP1</i> deficiency promoted CAC development in mice. Wild-type (WT) and <i>VDUP1</i> KO mice were used to investigate the role of VDUP1 in the development of azoxymethane (AOM)- and dextran sulfate sodium (DSS)-induced CAC. VDUP1 levels significantly decreased in the colonic tumor and adjacent nontumoral tissues of WT mice after AOM/DSS treatment. Moreover, AOM/DSS-treated <i>VDUP1</i> KO mice exhibited a worse survival rate, disease activity index, and tumor burden than WT mice. <i>VDUP1</i> deficiency significantly induced cell proliferation and anti-apoptosis in tumor tissues of <i>VDUP1</i> KO mice compared to WT littermates. Additionally, mRNA levels of interleukin-6 and tumor necrosis factor-alpha and active forms of signal transducer and activator of transcription 3 and nuclear factor-kappa B p65 were significantly increased in the tumor tissues of <i>VDUP1</i> KO mice. Overall, this study demonstrated that the loss of <i>VDUP1</i> promoted AOM/DSS-induced colon tumorigenesis in mice, highlighting the potential of VDUP1-targeting strategies for colon cancer prevention and treatment.