Related Experiment Video
Updated: Jan 16, 2026

In vitro Organoid Culture of Primary Mouse Colon Tumors
Published on: May 17, 2013
TRIM21 promotes colorectal cancer development through regulating DNA replication by TCF3/MCM2/5 axis
Xintian Zhang1, Han Yao1, Yichao Hou1
1Shanghai Key Laboratory of Gut Microecology and Associated Major Diseases Research, Digestive Disease Research and Clinical Translation Center, Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, 200011, Shanghai, China.
Abstract:
Disrupting DNA replication has been employed for treating cancers. In the present study, we found that Tripartite motif containing 21 (TRIM21) was highly expressed in colorectal cancer (CRC) and could be valuable for predicting the prognosis of CRC patients. Further study demonstrated that TRIM21 positively regulated the expression of MCM2 and MCM5, DNA replication and proliferation of CRC cells both in vitro and in vivo. In addition, TRIM21 knockdown inhibited both replication initiation and velocity, and increased the chemosensitivity of CRC cells to 5-FU and SN-38. Our study also revealed that DNA replication inhibition following TRIM21 knockdown could not be restored by cell cycle checkpoint kinase inhibitors, but partially by Transcription Factor 3 (TCF3) knockdown. TCF3 directly suppressed MCM2 and MCM5 transcription, inhibiting DNA replication. In summary, TRIM21 could influence tumor development and chemosensitivity to replication inhibitors by regulating DNA replication through the TCF3/MCM2/5 axis, suggesting a promising potential for CRC in the clinic.
Insights
Tripartite motif containing 21 (TRIM21) promotes colorectal cancer (CRC) cell growth by regulating DNA replication. Inhibiting TRIM21 enhances CRC chemosensitivity, offering a potential therapeutic strategy for this cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Disrupting DNA replication is a key strategy in cancer treatment.
- Colorectal cancer (CRC) remains a significant global health challenge.
- Identifying novel molecular targets for CRC therapy is crucial.
Purpose of the Study:
- To investigate the role of Tripartite motif containing 21 (TRIM21) in colorectal cancer (CRC).
- To determine the relationship between TRIM21 expression and CRC prognosis.
- To elucidate the mechanism by which TRIM21 affects CRC cell proliferation and chemosensitivity.
Main Methods:
- Quantitative analysis of TRIM21 expression in CRC tissues.
- In vitro and in vivo experiments involving TRIM21 knockdown in CRC cells.
- Assessment of DNA replication markers (MCM2, MCM5) and cell proliferation.
- Chemosensitivity assays with 5-FU and SN-38.
- Investigation of the TCF3/MCM2/5 axis.
Main Results:
- TRIM21 was highly expressed in CRC and correlated with poor prognosis.
- TRIM21 positively regulated MCM2 and MCM5 expression, promoting CRC cell proliferation.
- TRIM21 knockdown inhibited DNA replication and increased sensitivity to 5-FU and SN-38.
- TCF3 directly suppressed MCM2/5 transcription, and its knockdown partially restored DNA replication.
Conclusions:
- TRIM21 influences CRC development and chemosensitivity by regulating DNA replication via the TCF3/MCM2/5 pathway.
- TRIM21 represents a potential prognostic biomarker and therapeutic target for CRC.
- Targeting the TRIM21-TCF3-MCM axis could offer a novel approach for CRC treatment.
More Related Videos
Related Concept Videos
Abnormal Proliferation
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Replicative Cell Senescence
Negative Regulator Molecules

