Homo sapiens Genome sequencing and assembly
RNA sequencing (RNA-seq) was used to investigate the effects of G4-targeted photodynamic therapy (PDT) on key genes and signaling pathways in MDA-MB-231 cells. We performed an enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG). In the TPA-T-TO treatment group, the pathways related to G4-DNA structure played an important role in the proliferation and progression of tumor cells, especially in gene regulation, DNA replication and repair, and mitochondrial function. After PDT treatment, the affected genes are also involved in the signaling pathways of cell cycle regulation and oxidative stress response. Further analysis revealed that ROS (reactive oxygen species) widely affected downstream processes such as cell proliferation, differentiation, and stress response by activating MAPK and PI3K-AKT pathways. The activation of the MAPK signaling pathway is particularly significant, and ROS regulates the cell cycle and apoptosis processes by affecting the activity of related kinases in the MAPK family (such as ERK, JNK, p38), thereby affecting the survival and death of tumor cells. In addition, the activation of the PI3K-AKT pathway may also accelerate the occurrence of ferroptosis by regulating iron metabolism and lipid peroxidation. Gene set enrichment analysis (GSEA) further showed that compared with TPA-T-TO treatment alone, PDT treatment significantly up-regulated gene expression related to p53 signaling pathway regulation, oxidative stress response and FoxO transcription factor activity. In conclusion, the main signaling pathways affected by TPA-T-TO-mediated G4-targeting combined with photodynamic therapy include gene regulation, oxidative stress, mitochondrial dysfunction, autophagy, PI3K-AKT, MAPK signaling pathway, and ferroptosis. These complex signaling networks interact to promote the stress response and eventual death of tumor cells.