RESUMEN
BACKGROUND: Breast cancer (BC), the most prevalent malignancy in women globally, still lacks comprehensive research on its molecular targets and necessitates further investigation into the underlying molecular mechanisms driving its initiation and progression. METHODS: The GSE20685 Series Matrix File downloaded from the Gene Expression Omnibus database was divided into a high-risk group (n = 49) and a low-risk group (n = 278) to construct the co-expression network. RESULTS: Four hub genes were identified based on the Weighted Gene Co-expression Network Analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses were performed. Hub gene immune infiltration was investigated using the Tumor Immune Estimation Resource database, and CD4+ T cell expression levels were substantially correlated with hub gene expression. Based on the CancerRxGene database (Genomics of Drug Sensitivity in Cancer database), it was found that the hub genes were highly sensitive to common chemotherapy drugs such as AKT inhibitor VIII and Erlotinib. The expression of Secreted Frizzled-Related Protein 1, melanoma-inhibiting activity (MIA), and Keratin 14 was related to tumor mutation burden, and the expression of MIA also affected the microsatellite instability of the tumor. This study employs multi-omics analysis to investigate the molecular network associated with the prognosis of BC, highlighting its intricate connection with the immune microenvironment. CONCLUSION: These findings pinpoint four crucial genes in BC progression, offering targets for further research and therapy. Their connections to immune infiltration and chemotherapy sensitivity underscore complex interactions in the tumor microenvironment.
RESUMEN
@#Objective:To explore the mechanism by which SRY-related high mobility group-box 9 (SOX9) promotes the epithelial mesenchymal transition (EMT) of non-small cell lung cancer (NSCLC) A549 cells via the Wnt/β-catenin pathway. Methods: The human NSCLCA549 cell line was divided into three groups: OE-NC group, OE-SOX9 group and OE-SOX9+XAV-939 group. The cells in OESOX9 group were transfected with SOX9 pcDNA plasmid to up-regulate the expression level of SOX9; The cells in OE-SOX9+XAV939 group were transfected with SOX9 pcDNA plasmid while the β-catenin inhibitor XAV-939 (1.0 μmol/L) was added to the medium. qPCR was used to detect SOX9 mRNA levels; CCK-8 was used to examine the proliferation of A549 cells; Wound-healing assay and Transwell chamber assay were used to detect the migration and invasion ofA549 cells, respectively; and WB was used to detect protein expressions of SOX9, β-catenin, E-cadherin, γ-catenin, N-cadherin and vimentin. Results: The mRNA and protein levels of SOX9 in OE-SOX9 group and OE-SOX9+XAV-939 group were significantly higher than those in the OE-NC group after transfection (all P< 0.05), while there was no significant difference between the OE-SOX9 group and the OE-SOX9+XAV-939 group (P>0.05). The proliferation, migration and invasion of cells in OE-SOX9 group were significantly higher than those in OE-NC group; however, those abilities in OE-SOX9+XAV-939 group were significantly lower than those in OE-SOX9 group (all P<0.05). The level of β-catenin protein in OE-SOX9 group was significantly higher than that in the OE-NC group, while the level of β-catenin protein in OE-SOX9+XAV-939 group was lower than that in OE-SOX9 group (all P<0.05). Compared with the OE-NC group, the levels of phenotypic markers of epithelial cells, E-cadherin and γ-catenin, were down-regulated, and the phenotypic markers of mesenchymal cells, N-cadherin and vimentin, were up-regulated in cells of OE-SOX9 group; however, E-cadherin and γ-catenin were higher, and N-cadherin and vimentin were lower in OE-SOX9+XAV-939 group than those in OE-SOX9 group (all P<0.05). Conclusion: SOX9 could promote proliferation, migration and EMT of NSCLCA549 cells by activating the Wnt/β-catenin pathway. ··