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Updated: Nov 7, 2025
Methyl-binding DNA capture Sequencing for Patient Tissues
Published on: October 31, 2016
Genome-Wide Methylation Mapping Using Nanopore Sequencing Technology Identifies Novel Tumor Suppressor Genes in
Colin F Davenport1, Tobias Scheithauer1, Alessia Dunst2
1Research Core Unit Genomics OE 9415, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30623 Hannover, Germany.
Abstract:
Downregulation of multiple tumor suppressor genes (TSGs) plays an important role in cancer formation. Recent evidence has accumulated that cancer progression involves genome-wide alteration of epigenetic modifications, which may cause downregulation of the tumor suppressor gene. Using hepatocellular carcinoma (HCC) as a system, we mapped 5-methylcytosine signal at a genome-wide scale using nanopore sequencing technology to identify novel TSGs. Integration of methylation data with gene transcription profile of regenerated liver and primary HCCs allowed us to identify 10 potential tumor suppressor gene candidates. Subsequent validation led us to focus on functionally characterizing one candidate-glucokinase (GCK). We show here that overexpression of GCK inhibits the proliferation of HCC cells via induction of intracellular lactate accumulation and subsequently causes energy crisis due to NAD+ depletion. This suggests GCK functions as a tumor suppressor gene and may be involved in HCC development. In conclusion, these data provide valuable clues for further investigations of the process of tumorigenesis in human cancer.
Insights
Glucokinase (GCK) acts as a tumor suppressor gene in hepatocellular carcinoma (HCC). Its overexpression inhibits cancer cell proliferation by depleting cellular energy resources, offering new insights into cancer development.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Tumor suppressor genes (TSGs) downregulation is critical in cancer formation.
- Epigenetic modifications, including DNA methylation, are implicated in cancer progression and TSG silencing.
- Hepatocellular carcinoma (HCC) provides a model system to study these mechanisms.
Purpose of the Study:
- To identify novel tumor suppressor genes (TSGs) in hepatocellular carcinoma (HCC) using genome-wide epigenetic profiling.
- To functionally characterize the role of glucokinase (GCK) as a potential TSG in HCC.
Main Methods:
- Genome-wide 5-methylcytosine mapping using nanopore sequencing technology.
- Integration of methylation data with gene transcription profiles from regenerated liver and primary HCC tissues.
- Functional characterization of glucokinase (GCK) in HCC cell lines.
Main Results:
- Identified 10 potential TSG candidates by integrating methylation and transcription data.
- Demonstrated that glucokinase (GCK) overexpression inhibits HCC cell proliferation.
- Showed GCK overexpression induces intracellular lactate accumulation, leading to NAD+ depletion and energy crisis.
Conclusions:
- Glucokinase (GCK) functions as a tumor suppressor gene in HCC.
- GCK's mechanism involves inducing an energy crisis through lactate accumulation and NAD+ depletion.
- These findings offer valuable insights into tumorigenesis in human cancers, particularly HCC.
