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Updated: Sep 23, 2026
Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
Expression of DNA (5-cytosin)-methyltransferases (DNMTs) in hepatocellular carcinomas
Maho Nagai1, Akihiro Nakamura, Reiko Makino
1Second Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan
Abstract:
Down-regulation of tumor suppressor genes by hypermethylation of 5'-CpGs is one of the important mechanisms involved in tumor development. DNA (5-cytosine)-methyltransferases (DNMTs) are enzymes that methylate the cytosine residue of CpGs, and four types have been identified (DNMT1, 2, 3a and 3b). To examine the involvement of DNMTs in hepatocellular carcinogenesis, we measured DNMT mRNAs in hepatocellular carcinomas (HCCs). mRNAs of DNMT1, 2, 3a and 3b were detected by reverse transcription-PCR analysis and quantified by a real-time PCR method in surgically resected HCCs and adjacent non-tumorous liver tissue. DNMT1 was expressed in all tissues and at a significantly higher level in HCCs than in non-tumorous liver tissue (P=0.01). DNMT2 was expressed at a low level in all tissues. DNMT3a and DNMT3b mRNA were undetectable in normal liver. DNMT3a was expressed in all HCCs and was expressed at similar levels in 60% of the non-tumorous liver tissues. DNMT3b mRNA was detected at a significantly higher level (P=0.002) in HCCs than in non-tumorous liver tissues. The amount of DNMT1, 3a and 3b mRNA was not different between HCCs with or without hypermethylation of the CDH1 promoter. These data suggest that overexpression of DNMT1 and DNMT3b contributes to hepatocellular carcinogenesis.
Insights
Overexpression of DNA methyltransferases (DNMTs), specifically DNMT1 and DNMT3b, is linked to hepatocellular carcinoma (liver cancer) development. These enzymes play a role in the abnormal gene methylation driving cancer progression.
Area of Science:
- Molecular Biology
- Oncology
- Epigenetics
Background:
- Hypermethylation of CpG islands in tumor suppressor genes is a key mechanism in cancer development.
- DNA (cytosine-5)-methyltransferases (DNMTs) are responsible for adding methyl groups to DNA, influencing gene expression.
- Understanding the role of specific DNMTs in hepatocellular carcinogenesis is crucial for identifying potential therapeutic targets.
Purpose of the Study:
- To investigate the expression levels of DNMT1, DNMT2, DNMT3a, and DNMT3b mRNAs in hepatocellular carcinoma (HCC) tissues compared to adjacent non-tumorous liver tissues.
- To determine the correlation between DNMT expression and the hypermethylation status of the CDH1 promoter in HCC.
- To elucidate the contribution of DNMTs to the development of liver cancer.
Main Methods:
- Messenger RNA (mRNA) levels of DNMT1, DNMT2, DNMT3a, and DNMT3b were measured using reverse transcription-polymerase chain reaction (RT-PCR) and quantitative real-time PCR.
- Analysis was performed on surgically resected HCC samples and corresponding non-tumorous liver tissues.
- Hypermethylation of the CDH1 promoter was assessed in HCC samples.
Main Results:
- DNMT1 mRNA was significantly upregulated in HCC tissues compared to non-tumorous liver tissues (P=0.01).
- DNMT3b mRNA was also significantly elevated in HCC tissues (P=0.002).
- DNMT3a mRNA was detected in both HCC and some non-tumorous tissues, while DNMT2 showed low expression across all samples. No significant difference in DNMT1, 3a, or 3b mRNA levels was observed concerning CDH1 promoter hypermethylation.
Conclusions:
- The findings suggest that overexpression of DNMT1 and DNMT3b plays a significant role in hepatocellular carcinogenesis.
- These DNMTs may contribute to the epigenetic dysregulation observed in liver cancer.
- Further research into targeting DNMT1 and DNMT3b could offer new strategies for HCC treatment.
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