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Updated: Jan 9, 2026
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Targeted methylation of cg24067911 suppresses colorectal cancer metastasis through BCL6-ATXN1-CDH1 axis
Lu-Ping Yang1,2, Jia-Qian Huang1,2,3, Chiu-Wing Yeung1,2
1Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Abstract:
DNA methylation plays a crucial role in the progression and metastasis of colorectal cancer (CRC), yet the mechanisms underlying its effect at specific loci remain poorly understood. We previously identified cg24067911 hypomethylation as a potential biomarker associated with poor CRC prognosis. To investigate the role of cg24067911 methylation in CRC metastasis and elucidate its underlying molecular mechanisms, we utilized the CRISPR-dCas9-DNMT3a system to specifically modify the methylation status of cg24067911. Then, we performed high-throughput transposase-accessible chromatin sequencing, RNA sequencing, and chromatin immunoprecipitation analysis. We demonstrated that cg24067911 was located within an enhancer region of the ATXN1 gene, where it was bound by BCL6. Hypomethylation of cg24067911 improved the binding of BCL6 to this enhancer, leading to upregulated transcription of ATXN1. Furthermore, ATXN1 was found to act as a transcription factor that upregulates CDH2, promoting epithelial-mesenchymal transition and facilitating CRC metastasis. These findings not only reveal that cg24067911 methylation modulates CRC metastasis through a novel epigenetic mechanism involving ATXN1 and CDH2, but also highlight cg24067911 as a potential prognostic marker for CRC and suggest that targeted epigenetic therapies could be an effective strategy for treating CRC metastasis in the future.
Insights
DNA methylation at cg24067911 influences colorectal cancer (CRC) metastasis by regulating ATXN1 and CDH2. This epigenetic mechanism highlights cg24067911 as a potential prognostic marker for CRC.
Area of Science:
- Molecular Biology
- Cancer Epigenetics
- Genomics
Background:
- DNA methylation is critical in colorectal cancer (CRC) progression and metastasis.
- Specific mechanisms of DNA methylation at certain loci in CRC are not well understood.
- cg24067911 hypomethylation was previously identified as a potential biomarker for poor CRC prognosis.
Purpose of the Study:
- To investigate the role of cg24067911 methylation in CRC metastasis.
- To elucidate the molecular mechanisms by which cg24067911 affects CRC metastasis.
- To explore cg24067911 as a potential prognostic marker and therapeutic target.
Main Methods:
- CRISPR-dCas9-DNMT3a system for targeted methylation modification of cg24067911.
- High-throughput transposase-accessible chromatin sequencing (ATAC-seq).
- RNA sequencing (RNA-seq) and chromatin immunoprecipitation (ChIP) analysis.
Main Results:
- cg24067911 is located in an enhancer region of the ATXN1 gene and binds BCL6.
- Hypomethylation of cg24067911 enhances BCL6 binding, upregulating ATXN1 transcription.
- ATXN1 acts as a transcription factor, upregulating CDH2, promoting epithelial-mesenchymal transition (EMT), and facilitating CRC metastasis.
Conclusions:
- cg24067911 methylation modulates CRC metastasis via a novel epigenetic pathway involving ATXN1 and CDH2.
- cg24067911 serves as a potential prognostic biomarker for colorectal cancer.
- Targeted epigenetic therapies may offer a future strategy for treating CRC metastasis.
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