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- Title
Vitamin D 3 Upregulated Protein 1 Deficiency Promotes Azoxymethane/Dextran Sulfate Sodium-Induced Colorectal Carcinogenesis in Mice.
- Authors
Park, Ki Hwan; Kim, Hyoung-Chin; Won, Young-Suk; Yoon, Won Kee; Choi, Inpyo; Han, Sang-Bae; Kang, Jong Soon
- Abstract
Simple Summary: Inflammatory bowel disease (IBD) increases the risk of developing colitis-associated colorectal cancer (CAC) compared to the general population. The specific genetic alterations associated with the onset of CAC are largely unknown. In this study, we investigated the role of vitamin D3 upregulated protein 1 (VDUP1) in a CAC mouse model. VDUP1 knockout (KO) increased the severity of colitis and CAC development. Our data suggest that VDUP1 may be explored as a potential therapeutic approach for CAC prevention. 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 VDUP1 deficiency on CAC remain unclear. In this study, we found that VDUP1 deficiency promoted CAC development in mice. Wild-type (WT) and VDUP1 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 VDUP1 KO mice exhibited a worse survival rate, disease activity index, and tumor burden than WT mice. VDUP1 deficiency significantly induced cell proliferation and anti-apoptosis in tumor tissues of VDUP1 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 VDUP1 KO mice. Overall, this study demonstrated that the loss of VDUP1 promoted AOM/DSS-induced colon tumorigenesis in mice, highlighting the potential of VDUP1-targeting strategies for colon cancer prevention and treatment.
- Subjects
PROTEINS; RESEARCH funding; CELL proliferation; APOPTOSIS; COLORECTAL cancer; CANCER patients; DESCRIPTIVE statistics; CHOLECALCIFEROL; POLYSACCHARIDES; MICE; ANIMAL experimentation; ORGANIC compounds; STAT proteins; TUMOR necrosis factors
- Publication
Cancers, 2024, Vol 16, Issue 17, p2934
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers16172934