<p>Cell-free DNA (cfDNA) attracts increasing attention not only as a diagnostic tool for tumor resistance to cytostatic therapy, but also as an active participant of the tumor process. GC-rich DNA accumulates in the cfDNA pool and stimulates TLR9/MyD88/NF-κB signaling, thereby increasing the expression of genes responsible for viability of cancer cells. We studied the effect of GC-DNA on the transcriptional activity of survival genes in wild-type MCF7 cells (wt MCF7) and <i>TLR9</i> gene knockout MCF7 cells (<i>TLR9</i>–/– MCF7). It was shown that, in contrast to wt MCF7 cell cultures, <i>TLR9</i>–/– MCF7 cells responded to stimulation with GC-DNA fragments by a decrease in the activity of TLR9/MyD88/NF-κB signaling cascade and a decline in survival gene expression. Our data indicate that TLR9/MyD88/NF-κB signaling cascade components may be considered as potential targets for cancer therapy.</p>

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GC-Reach DNA Fragments Reduce the Expression of Survival Genes in MCF7 Breast Carcinoma Cells: TLR9/MyD88/NF-κB Signaling Pathway as a Potential Target for Cancer Therapy

  • E. M. Malinovskaya,
  • G. V. Shmarina,
  • E. S. Ershova,
  • L. V. Kameneva,
  • N. N. Veiko,
  • V. P. Veiko,
  • M. S. Konkova,
  • P. A. Bobrovsky,
  • E. A. Kozhina,
  • P. E. Umriukhin,
  • V. N. Lazarev,
  • A. Y. Asanov,
  • T. M. Rozhnova,
  • V. N. Nikolenko,
  • M. Y. Sinelnikov,
  • S. V. Kostyuk

摘要

Cell-free DNA (cfDNA) attracts increasing attention not only as a diagnostic tool for tumor resistance to cytostatic therapy, but also as an active participant of the tumor process. GC-rich DNA accumulates in the cfDNA pool and stimulates TLR9/MyD88/NF-κB signaling, thereby increasing the expression of genes responsible for viability of cancer cells. We studied the effect of GC-DNA on the transcriptional activity of survival genes in wild-type MCF7 cells (wt MCF7) and TLR9 gene knockout MCF7 cells (TLR9–/– MCF7). It was shown that, in contrast to wt MCF7 cell cultures, TLR9–/– MCF7 cells responded to stimulation with GC-DNA fragments by a decrease in the activity of TLR9/MyD88/NF-κB signaling cascade and a decline in survival gene expression. Our data indicate that TLR9/MyD88/NF-κB signaling cascade components may be considered as potential targets for cancer therapy.