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Updated: Dec 10, 2025
In vitro Organoid Culture of Primary Mouse Colon Tumors
Published on: May 17, 2013
TRIM21 Is Decreased in Colitis-associated Cancer and Negatively Regulates Epithelial Carcinogenesis
Guangxi Zhou1,2, Huili Wu3, Jian Lin1
1Department of Gastroenterology, The Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
Background:
Tripartite motif-containing (TRIM)21 is reported to be associated with the regulation of immune response in gut mucosa. Here we studied the underlying mechanisms of TRIM21 in the pathogenesis of colitis-associated cancer (CAC).
Methods:
We analyzed TRIM21 expression in tumor tissues from patients with colorectal cancer (CRC) and ulcerative colitis (UC)-associated cancer by immunohistochemistry and real-time polymerase chain reaction and established a CAC model in TRIM21-∕- and wild type mice by azoxymethane (AOM) and dextran sodium sulfate (DSS). Associated gene expression of tumor cell proliferation, adhesion, tissue remodeling and angiogenesis, and inflammatory cytokines were examined in normal colon and CAC by immunohistochemistry and real-time polymerase chain reaction.
Results:
Expression of TRIM21 was found to be decreased in tumor tissues from patients with CRC and UC-associated cancer than that in controls, and TRIM21-∕- deficiency promoted AOM/DSS-induced CAC, characterized by more weight loss and multiple, large colon tumors in TRIM21-∕- mice. Moreover, associated gene expression of tumor cell proliferation (eg, Ki67), tissue remodeling and angiogenesis (eg, MMP10, HIF1-α, COX2, Ang4), and pro-inflammatory cytokines (eg, IL-6, TNF-α, IL-1β) markedly upregulated, whereas associated gene expression of tumor cell adhesion (E-cadherin) and inflammatory cytokines (eg, IL-10, TGF-β, Foxp3, IFN-γ) downregulated in tumor tissues from TRIM21-/- mice compared with controls.
Conclusions:
TRIM21 is decreased in colitis-associated cancer and negatively regulates intestinal epithelial carcinogenesis by modulating epithelial cell proliferation, adhesion, tissue remodeling and angiogenesis, and pro-inflammatory responses. Therefore, TRIM21 may serve as a novel therapeutic target for CAC therapy.
Insights
Tripartite motif-containing (TRIM)21 is decreased in colitis-associated cancer (CAC). TRIM21 deficiency promotes intestinal carcinogenesis by affecting cell proliferation, adhesion, and inflammation, suggesting it as a therapeutic target.
Area of Science:
- Gastroenterology
- Oncology
- Immunology
Background:
- Tripartite motif-containing (TRIM)21 regulates immune responses in the gut.
- Its role in colitis-associated cancer (CAC) pathogenesis requires elucidation.
Purpose of the Study:
- To investigate the mechanisms of TRIM21 in CAC pathogenesis.
- To evaluate TRIM21 as a potential therapeutic target for CAC.
Main Methods:
- TRIM21 expression analyzed in human colorectal cancer (CRC) and ulcerative colitis (UC)-associated cancer tissues.
- A CAC mouse model established using azoxymethane (AOM) and dextran sodium sulfate (DSS) in TRIM21-deficient and wild-type mice.
- Gene expression related to cell proliferation, adhesion, tissue remodeling, angiogenesis, and cytokines examined.
Main Results:
- TRIM21 expression was reduced in tumor tissues of CRC and UC-associated cancer patients.
- TRIM21 deficiency exacerbated AOM/DSS-induced CAC, leading to increased tumor burden.
- Key genes involved in proliferation, angiogenesis, and inflammation were upregulated in TRIM21-deficient mice, while adhesion molecules and certain anti-inflammatory cytokines were downregulated.
Conclusions:
- TRIM21 is downregulated in CAC and negatively regulates intestinal carcinogenesis.
- TRIM21 modulates epithelial cell proliferation, adhesion, tissue remodeling, angiogenesis, and inflammatory responses.
- TRIM21 represents a potential novel therapeutic target for CAC.
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