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GC-Reach DNA Fragments Reduce the Expression of Survival Genes in MCF7 Breast Carcinoma Cells: TLR9/MyD88/NF-κB

E M Malinovskaya1, G V Shmarina1, E S Ershova1

  • 1Research Centre for Medical Genetics, Moscow, Russia.

Bulletin of Experimental Biology and Medicine
|March 26, 2025
PubMed

Insights

GC-rich cell-free DNA (cfDNA) activates cancer cell survival pathways via TLR9 signaling. Blocking this pathway in knockout cells reduced survival gene expression, suggesting therapeutic potential.

Area of Science:

  • Molecular Biology
  • Immunology
  • Oncology

Background:

  • Cell-free DNA (cfDNA) is implicated in cancer progression.
  • GC-rich cfDNA can activate immune signaling pathways.
  • Toll-like receptor 9 (TLR9) signaling is involved in cancer cell survival.

Purpose of the Study:

  • To investigate the role of GC-rich cfDNA in cancer cell survival.
  • To determine the involvement of the TLR9/MyD88/NF-κB signaling cascade in this process.
  • To compare the response of wild-type and TLR9-deficient cancer cells to GC-DNA stimulation.

Main Methods:

  • Utilized wild-type MCF7 (wt MCF7) and TLR9 gene knockout MCF7 (TLR9-/- MCF7) cell lines.
  • Stimulated cells with GC-rich DNA fragments.
  • Measured transcriptional activity of survival genes.
  • Assessed the activity of the TLR9/MyD88/NF-κB signaling cascade.

Main Results:

  • Wild-type MCF7 cells showed increased survival gene expression upon GC-DNA stimulation.
  • TLR9-/- MCF7 cells exhibited decreased TLR9/MyD88/NF-κB signaling activity.
  • TLR9-/- MCF7 cells showed a decline in survival gene expression compared to wt MCF7 cells.

Conclusions:

  • The TLR9/MyD88/NF-κB signaling cascade mediates the pro-survival effects of GC-rich cfDNA in cancer cells.
  • TLR9 signaling is crucial for GC-DNA-induced cancer cell viability.
  • Components of the TLR9/MyD88/NF-κB pathway represent potential therapeutic targets for cancer treatment.
Keywords:
TLR9/MyD88/NF-κB signaling pathwayadaptationcell-free DNA (cfDNA)tumor

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