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.

Abstract

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.