MDA-MB-231 Genome sequencing and assembly
The study examined the differentially expressed genes (DEGs) between cells treated with small molecule ligands and untreated cells using MDA-MB-231 cells. A total of 2857 DEGs were identified using the screening criteria of >2.0 fold change and FDR<0.05. Of these, 1174 genes were up-regulated and 1683 genes were down-regulated. The differentially expressed genes (DEGs) were analysed using Gene Ontology (GO) and Kyoto Encyclopedia of the Genome (KEGG) to evaluate the impact of small molecule ligands on the activity and function of MDA-MB-231 cells, and to investigate potential activation pathways. The GO enrichment analysis revealed significant down-regulation of DEGs in three areas: biological processes, cellular components, and molecular functions. The analysis revealed that small molecule ligands mainly exert anti-tumor effects by inhibiting cell proliferation. This is supported by the enrichment of key processes related to cell proliferation, such as chromosome segregation, DNA replication, and cell cycle. The KEGG pathway enrichment analysis results were consistent with those of the GO enrichment analysis, which showed significant down-regulation of the DNA replication and cell cycle signaling pathways. Furthermore, numerous apoptosis-related signaling pathways were significantly upregulated, including calcium, TNF, FoxO, INF-1, JAK-STAT, Necroptosis, and cMAP. Additionally, small molecule ligands inhibited the anti-apoptotic Hippo signaling pathway and the Rap1 signaling pathway, which promotes cell survival and proliferation. The study found that small molecule ligands induce apoptosis in MDA-MB-231 cells. Additionally, the upregulation of the glycolysis/glycolysis signaling pathway was observed, indicating that the small molecule ligands affected the mitochondrial function of the cells. The cells compensated for the energy deficit caused by the decreased mitochondrial function by increasing the glycolytic pathway. Simultaneously, small molecule ligands induce mitochondrial autophagy via the FoxO signalling pathway. Additionally, KEGG enrichment analysis indicates a significant upregulation in the expression of core genes related to cellular senescence and iron metabolism. This suggests that small molecule ligands disrupt cellular energy and iron metabolism, leading to accelerated cellular senescence and iron death. Taken together, the findings suggest that small molecule ligands have antitumor effects by inhibiting cell proliferation, interfering with cellular mitochondrial function, promoting apoptosis, and regulating cellular energy and iron metabolism.