Malinovskaya E M, Shmarina G V, Ershova E S, Kameneva L V, Veiko N N, Veiko V P, Konkova M S, Bobrovsky P A, Kozhina E A, Umriukhin P E, Lazarev V N, Asanov A Y, Rozhnova T M, Nikolenko V N, Sinelnikov M Y, Kostyuk S V
Research Centre for Medical Genetics, Moscow, Russia.
Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical-Biological Agency of Russia, Moscow, Russia.
Bull Exp Biol Med. 2025 Feb;178(4):467-472. doi: 10.1007/s10517-025-06357-3. Epub 2025 Mar 26.
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.
游离DNA（cfDNA）不仅作为肿瘤对细胞抑制疗法耐药性的诊断工具，而且作为肿瘤进程的积极参与者，正吸引着越来越多的关注。富含鸟嘌呤-胞嘧啶（GC）的DNA在cfDNA池中积累，并刺激Toll样受体9（TLR9）/髓样分化因子88（MyD88）/核因子κB（NF-κB）信号通路，从而增加负责癌细胞存活的基因的表达。我们研究了GC-DNA对野生型MCF7细胞（wt MCF7）和TLR9基因敲除的MCF7细胞（TLR9-/- MCF7）中存活基因转录活性的影响。结果表明，与wt MCF7细胞培养物不同，TLR9-/- MCF7细胞对GC-DNA片段刺激的反应是TLR9/MyD88/NF-κB信号级联活性降低和存活基因表达下降。我们的数据表明，TLR9/MyD88/NF-κB信号级联成分可被视为癌症治疗的潜在靶点。
