期刊
CANCERS
卷 14, 期 19, 页码 -出版社
MDPI
DOI: 10.3390/cancers14194639
关键词
ovarian cancer; platinum resistance; NR2F1; TGF-beta 1; EMT; CAF
类别
资金
- Science and Technology Innovation Program of Hunan Province [2021RC3029]
- China Postdoctoral Science Foundation [2021T140754, 2020M672521]
- Postdoctoral Science Foundation of Central South University [248485]
- Fundamental Research Funds for the Central Universities of Central South University [2022ZZTS0946]
NR2F1 regulates platinum sensitivity and immune response in ovarian cancer by modulating TGF-beta 1-mediated EMT.
The mechanism underlying platinum resistance in ovarian cancer (OC) remains unclear. We used bioinformatic analyses to screen differentially expressed genes responsible for platinum resistance and explore NR2F1's correlation with prognostic implication and OC staging. Moreover, Gene-set enrichment analysis (GSEA) and Gene Ontology (GO) analyses were used for pathway analysis. Epithelial-mesenchymal transition (EMT) properties, invasion, and migration capacities were analyzed by biochemical methods. The association between NR2F1 and cancer-associated fibroblast (CAF) infiltration and immunotherapeutic responses were also researched. A total of 13 co-upregulated genes and one co-downregulated gene were obtained. Among them, NR2F1 revealed the highest correlation with a poor prognosis and positively correlated with OC staging. GSEA and GO analysis suggested the induction of EMT via TGF beta-1 might be a possible mechanism that NR2F1 participates in resistance. In vitro experiments showed that NR2F1 knockdown did not affect cell proliferation, but suppressed cell invasion and migration with or without cisplatin treatment through the EMT pathway. We also found that NR2F1 could regulate TGF-beta 1 signaling, and treating with TGF-beta 1 could reverse these effects. Additionally, NR2F1 was predominantly associated with immunosuppressive CAF infiltration, which might cause a poor response to immune check blockades. In conclusion, NR2F1 regulates TGF-beta 1-mediated EMT affecting platinum sensitivity and immune response in OC patients.
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