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Updated: Jan 26, 2026
Methylated DNA Immunoprecipitation
Published on: January 2, 2009
JAM3 functions as a novel tumor suppressor and is inactivated by DNA methylation in colorectal cancer
Dan Zhou1,2,3, Weiwei Tang4, Yun Zhang1,2,3
1Department of Medical Oncology, Xiang'an Hospital of Xiamen University, Xiamen, Fujian, China, anhanxiang@xmu.edu.cn; zhangy@fjirsm.ac.cn.
Purpose:
JAM3, an adhesion and transmigration regulatory element, is abundantly expressed in intestinal epithelial cells. However, its expression and function in colorectal cancer (CRC) remain unknown. In this study, we explored its epigenetic mechanism and biological role in CRC.
Patients And Methods:
Bioinformatics analysis was used to analyze the expression and methylation level of JAM3 in CRC. Methylation and expression status of JAM3 were then validated by quantitative methylation-specific PCR (qMSP) and quantitative PCR in tissues, plasma samples, and cell lines. Flow cytometry, Western blot, transwell, siRNA, colony formation, and transfection were used to evaluate the biological function of JAM3.
Results:
We initially found that JAM3 was frequently methylated and downregulated in CRC based on bioinformatics tools. qMSP validation showed that the methylation levels of JAM3 were increased in 75% (18/24) of CRC tissues, 61% (11/18) plasma samples, and all four CRC cell lines and were significantly associated with tumor stage in CRC tissues. Moreover, JAM3 was downregulated in primary CRC tissues, plasma samples, and CRC cell lines as compared with that in nonmalignant controls, although its expression could be recovered after demethylation treatment. Restoration of JAM3 repressed CRC cell viability, colony formation, and migration. In addition, siRNA-mediated depletion of JAM3 in NCM460 cells improved the clonogenicity and migration capability, whereas it suppressed cell apoptosis and cell-cycle arrest. These functional effects were accompanied with alterations of several epithelial cell markers, including E-cadherin, vimentin, phosphor-β-catenin (ser552), and TJP1, which were responsible for epithelial-mesenchymal transition.
Conclusion:
The findings indicated that JAM3 may be a novel tumor suppressor gene with epigenetic reduction in CRC and can be used as a potential noninvasive biomarker for CRC diagnosis.
Insights
Junctional Adhesion Molecule 3 (JAM3) is epigenetically silenced and downregulated in colorectal cancer (CRC), acting as a tumor suppressor. This JAM3 reduction offers potential as a noninvasive biomarker for CRC diagnosis.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Junction Adhesion Molecule 3 (JAM3) is crucial for intestinal epithelial cell adhesion and transmigration.
- The expression and function of JAM3 in colorectal cancer (CRC) are not well understood.
- Investigating JAM3's role in CRC is essential for understanding cancer development and identifying new biomarkers.
Purpose of the Study:
- To explore the epigenetic mechanism and biological role of JAM3 in colorectal cancer (CRC).
- To determine if JAM3 methylation and expression changes are associated with CRC development and progression.
- To evaluate JAM3's potential as a noninvasive diagnostic biomarker for CRC.
Main Methods:
- Bioinformatics analysis to assess JAM3 expression and methylation in CRC.
- Quantitative methylation-specific PCR (qMSP) and quantitative PCR for validation in tissues, plasma, and cell lines.
- Functional assays including flow cytometry, Western blot, transwell, siRNA, and colony formation to evaluate JAM3's biological role.
Main Results:
- JAM3 was frequently methylated and downregulated in CRC tissues, plasma, and cell lines.
- Increased JAM3 methylation correlated significantly with advanced tumor stage in CRC.
- Restoring JAM3 expression suppressed CRC cell viability, migration, and colony formation, indicating a tumor-suppressive role.
- JAM3 alterations were linked to changes in epithelial-mesenchymal transition markers.
Conclusions:
- JAM3 functions as a tumor suppressor gene in CRC, with its silencing primarily driven by epigenetic mechanisms.
- Epigenetic reduction of JAM3 is a significant event in colorectal cancer development.
- JAM3 represents a promising noninvasive biomarker for CRC diagnosis and potentially for monitoring disease progression.
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