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Updated: Jun 24, 2025

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
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Systematic Characterization of DNA Methyltransferases Family in Tumor Progression and Antitumor Immunity

Fengru Huang1, Xinyi Wu2, Qiong Du1

  • 1Department of Pharmacy, Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.

Technology in Cancer Research & Treatment
|June 7, 2024
PubMed

Insights

DNA methyltransferases (DNMTs) impact cancer progression and immunotherapy. This study reveals DNMT genes as key prognostic factors and potential therapeutic targets across diverse cancers, influencing the tumor microenvironment and immune response.

Area of Science:

  • Epigenetics and Cancer Biology
  • Molecular Oncology
  • Immunotherapy

Background:

  • DNA methylation, regulated by DNA methyltransferases (DNMTs), is crucial in cancer development.
  • Limited integrated analyses exist on DNMTs' roles in cancer stemness, tumor microenvironment (TME), and immunotherapy biomarkers.
  • Understanding DNMT family gene functions is vital for advancing cancer treatment strategies.

Purpose of the Study:

  • To comprehensively analyze the impact of five DNMT family genes (DNMT1, DNMT3A, DNMT3B, TRDMT1, DNMT3L) across 31 cancer types.
  • To investigate the association of DNMTs with transcriptional profiles, prognosis, cell stemness, TME, and immunotherapy biomarkers.
  • To validate the functional role of DNMT1 in cancer cell behavior.

Main Methods:

  • Utilized public databases to analyze DNMT gene expression, prognostic significance, and correlations with clinical and immunological features.
  • Assessed associations with Ki67, epithelial-mesenchymal transition (EMT) signatures, stemness scores, TME components (immune, stromal, ESTIMATE), and immune checkpoint markers (PDCD1, CTLA4).
  • Performed in vitro knockdown experiments for DNMT1 in MCF-7 and HepG2-C3A cell lines to evaluate its functional impact on proliferation and migration.

Main Results:

  • DNMT1, DNMT3A, and DNMT3B expression were elevated in most cancers, while TRDMT1 and DNMT3L expression decreased.
  • DNMT family genes significantly correlated with patient prognosis, TME composition, and immune cell infiltration.
  • Expression of DNMT1, DNMT3A, and DNMT3B showed notable associations with immune checkpoint genes PDCD1 and CTLA4.
  • DNMT1 knockdown reduced cancer cell proliferation and migration in vitro.

Conclusions:

  • DNMT family genes are significant prognostic indicators in a wide range of cancers.
  • DNMTs play a critical role in shaping the tumor microenvironment and influencing immune responses.
  • DNMTs represent promising therapeutic targets for enhancing cancer immunotherapy efficacy.
Keywords:
DNMT familyimmunomodulatorsprognosistumor microenvironmentvarious cancers

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