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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Identification and investigation of methylated genes in hepatoma
Tetsuhiro Chiba1, Osamu Yokosuka, Kenichi Fukai
1Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo Ward, Chiba 260-8670, Japan.
Abstract:
Gene silencing due to aberrant DNA methylation plays an important role in carcinogenesis. Previous microarray analysis demonstrated that 14 genes, including hepatocyte growth factor activator inhibitor 2/placental bikunin (HAI2/PB) gene, showed particularly high inductions after 5-aza-2'deoxycytidine (5Aza-dC) treatment in multiple hepatoma cell lines. In the present study, we studied all of these genes except for the HAI2/PB gene and examined DNA methylation status and levels of acetylated histones using bisulphite genomic sequencing and the chromatin immunoprecipitation (ChIP) assay, respectively. Aberrant methylation in primary hepatoma tissues was also examined using methylation-specific polymerase chain reaction (MSP). Genes for E-cadherin, collagen type I alpha 2 (COL1A2), insulin-like growth factor binding protein 2 (IGFBP2), connective tissue growth factor (CTGF) and fibronectin 1 exhibited aberrant methylation in several hepatoma cell lines. The ChIP assay showed that DNA methylation and deacetylation of histones generally coexist except for fibronectin 1. In further studies of 24 primary hepatoma tissues, methylation signals for COL1A2, IGFBP2, CTGF and fibronectin 1 were detected in 13, 18, 4 and 10 patients, respectively. In conclusion, aberrant methylation of COL1A2, IGFBP2, CTGF and fibronectin 1 genes were detected in hepatoma cell lines. We also demonstrated that the methylation of 5'CpG islands and histone deacetylation generally coexisted in the regulation of gene expression except for fibronectin 1. The results of MSP in hepatoma tissues suggested that some of these genes might be involved in the development or progression of hepatoma.
Insights
Aberrant DNA methylation silences genes in hepatoma. Researchers found methylation in COL1A2, IGFBP2, CTGF, and fibronectin 1 genes in hepatoma cell lines and tissues, suggesting their role in liver cancer development.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Aberrant DNA methylation is a key mechanism in cancer development.
- Previous studies identified 14 genes induced by 5-aza-2'deoxycytidine (5Aza-dC) in hepatoma cell lines, indicating potential roles in liver cancer.
Purpose of the Study:
- To investigate the DNA methylation status and histone acetylation of specific genes in hepatoma.
- To determine if these epigenetic alterations are present in primary hepatoma tissues and correlate with cancer progression.
Main Methods:
- Bisulphite genomic sequencing and chromatin immunoprecipitation (ChIP) assays were used to analyze DNA methylation and histone acetylation in hepatoma cell lines.
- Methylation-specific polymerase chain reaction (MSP) was employed to detect aberrant methylation in 24 primary hepatoma tissues.
Main Results:
- Aberrant DNA methylation was observed in collagen type I alpha 2 (COL1A2), insulin-like growth factor binding protein 2 (IGFBP2), connective tissue growth factor (CTGF), and fibronectin 1 genes in hepatoma cell lines.
- DNA methylation and histone deacetylation generally coexisted, except for fibronectin 1.
- Methylation signals for COL1A2, IGFBP2, CTGF, and fibronectin 1 were detected in a significant proportion of primary hepatoma tissues.
Conclusions:
- Aberrant methylation of COL1A2, IGFBP2, CTGF, and fibronectin 1 genes is a common epigenetic event in hepatoma.
- The interplay between DNA methylation and histone deacetylation plays a role in regulating gene expression in liver cancer.
- These findings suggest that the investigated genes may be involved in the pathogenesis of hepatoma.
