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Updated: May 18, 2026

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
MPP3 inactivation by promoter CpG islands hypermethylation in colorectal carcinogenesis
Xiao Feng1, Kequan Chen, Shicai Ye
1Department of Gastroenterology, the Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China.
Background:
The Drosophila discs large tumor suppressor homologue-3 (MPP3), a putative tumor suppressor involved in cell adhesion and cell polarity, is frequently inactivated in several carcinomas due to promoter hypermethylation. The alteration of MPP3 methylation in colorectal carcinogenesis has not been investigated.
Objective:
To determine the role of inactivated MPP3 in colorectal tumorigenesis and the potential clinical application as a novel epigenetic marker.
Methods:
We measured MPP3 mRNA expression and promoter methylation in 6 colorectal cancer cell lines, 23 primary colorectal carcinomas and corresponding non-cancerous tissues. The correlations between MPP3 expression, DNA methylation and clinicopathological characteristics were evaluated.
Results:
Loss of MPP3 expression was observed in 2 of 6 (33.3%) colorectal cancer cell lines and 10 of 23 (43.5%) primary colorectal carcinomas. MPP3 promoter hypermethylation also occurred in the same colorectal cancer cell lines (SW1116 and LoVo) and 9 of 23 (39.1%) primary colorectal carcinomas. Among tumors loss of MPP3 mRNA expression, the promoter hypermethylation rate was 80%, which was significantly higher than tumors with over-expressed MPP3 (7.7%, P=0.001). After treated with 5-aza-dC, two cell lines (SW1116 and LoVo) revealed significant restoration of MPP3 expression. MPP3 promoter methylation was also significantly higher in advanced colorectal carcinoma (57.1%) compared with early stage tumor (11.1%).
Conclusion:
These preliminary data suggested that epigenetic inactivation of MPP3 frequently occurred during the development of colorectal cancer and might also be a potential biomarker for molecular classification of colorectal cancer patients.
Insights
Epigenetic inactivation of the tumor suppressor MPP3 occurs frequently in colorectal cancer, suggesting its potential as a novel biomarker for molecular classification.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- The tumor suppressor gene MPP3 (Drosophila discs large tumor suppressor homologue-3) is frequently inactivated in carcinomas via promoter hypermethylation.
- The role of MPP3 alterations in colorectal carcinogenesis remains uninvestigated.
Purpose of the Study:
- To investigate the role of MPP3 inactivation in colorectal tumorigenesis.
- To evaluate MPP3 as a potential epigenetic biomarker for colorectal cancer.
Main Methods:
- MPP3 mRNA expression and promoter methylation were analyzed in colorectal cancer cell lines and primary tumors.
- Correlations between MPP3 expression, DNA methylation, and clinicopathological features were assessed.
Main Results:
- MPP3 expression loss was observed in 33.3% of cell lines and 43.5% of primary colorectal carcinomas.
- MPP3 promoter hypermethylation correlated significantly with reduced expression (80% vs 7.7%) and advanced tumor stage (57.1% vs 11.1%).
- Re-expression of MPP3 was observed upon treatment with 5-aza-dC, confirming epigenetic silencing.
Conclusions:
- Epigenetic inactivation of MPP3 is a frequent event in colorectal cancer development.
- MPP3 may serve as a valuable biomarker for the molecular classification of colorectal cancer patients.
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