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Screening of Tumor Suppressor Genes in Metastatic Colorectal Cancer
Lu Qi1, Yanqing Ding1,2
1Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Abstract:
Most tumor suppressor genes are commonly inactivated in the development of colorectal cancer (CRC). The activation of tumor suppressor genes may be beneficial to suppress the development and metastasis of CRC. This study analyzed genes expression and methylation levels in different stages of CRC. Genes with downregulated mRNA expression and upregulated methylation level in advanced CRC were screened as the potential tumor suppressor genes. After comparing the methylation level of screened genes, we found that MBD1 gene had downregulated mRNA expression and upregulated methylation levels in advanced CRC and continuously upregulated methylation level in the progression of CRC. Enrichment analysis revealed that genes expression in accordance with the elevated expression of MBD1 mainly located on chromosomes 17p13 and 17p12 and 8 tumor suppressor genes located on chromosome 17p13. Further enrichment analysis of transcription factor binding site identified that SP1 binding site had higher enrichment and could bind with MBD1. In conclusion, MBD1 may be a tumor suppressor gene in advanced CRC and affect the development and metastasis of CRC by regulating 8 tumor suppressor genes through binding with SP1.
Insights
Methyl-CpG binding domain protein 1 (MBD1) may act as a tumor suppressor in colorectal cancer (CRC). It shows decreased expression and increased methylation in advanced CRC, potentially regulating other tumor suppressor genes.
Area of Science:
- Molecular Oncology
- Cancer Genomics
- Epigenetics
Background:
- Colorectal cancer (CRC) development is often linked to the inactivation of tumor suppressor genes.
- Reactivating tumor suppressor genes could potentially inhibit CRC progression and metastasis.
Purpose of the Study:
- To identify potential tumor suppressor genes in colorectal cancer (CRC) by analyzing gene expression and methylation patterns.
- To investigate the role of the MBD1 gene in CRC development and metastasis.
Main Methods:
- Analysis of gene expression and DNA methylation levels across different stages of colorectal cancer (CRC).
- Screening for genes with downregulated mRNA and upregulated methylation in advanced CRC.
- Enrichment analysis to identify associated gene locations and transcription factor binding sites, including SP1.
Main Results:
- The MBD1 gene exhibited downregulated mRNA expression and upregulated methylation in advanced CRC, with continuously increasing methylation during disease progression.
- Genes co-expressed with MBD1 were predominantly located on chromosomes 17p13 and 17p12, including 8 known tumor suppressor genes on 17p13.
- Enrichment analysis identified SP1 binding sites as highly enriched and capable of binding with MBD1.
Conclusions:
- MBD1 is proposed as a potential tumor suppressor gene in advanced colorectal cancer (CRC).
- MBD1 may influence CRC development and metastasis by regulating 8 tumor suppressor genes via interaction with the SP1 transcription factor.
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