Исследование с применением системы редактирования генома CRISPR/Cas9 биологического действия ГЦ-богатых последовательностей внеклеточной ДНК на процесс регуляции транскрипционной активности ДНК-сенсоров TLR9 и AIM2 в клетках линии MCF7

A number of diseases, including cancer, are associated with accumulation of GC-enriched sequences in the general cell-free DNA (cfDNA) pool. This fact is primarily explained by these DNA fragments increased resistance to the blood nucleases which can activate DNA sensors - TLR9 and AIM2 that have a different effect on the cancer cells functioning. The aim of the present study was to study the MCF 7 cells biological response to GC-rich cfDNA sequences and using AIM2 and TLR9 knockout to identify the functional role of DNA-binding receptors in the development of cellular adaptive response. It was experimentally established that MCF7 culture cells with TLR9 and AIM2 receptors “turned off” respond to stimulation by GC-DNA fragments by reducing the transcriptional activity of the genes of the TLR9/MYD88/NF-KBsignaling pathway and associated STAT 3/6 signaling pathways that increase the survival of cancer cells. This shows the need for further studies of the role of other genes, including on the example of cell lines with TLR9 and AIM2 knockout, in terms of detailing the mechanisms of the effects noted in this work on cancer cell survival.