基因敲除
癌症研究
上皮-间质转换
卵巢癌
免疫系统
转化生长因子
顺铂
生物
癌症
肿瘤科
医学
内科学
基因
免疫学
转移
内分泌学
化疗
遗传学
作者
Qiuju Liang,Zhijie Xu,Yuanhong Liu,Bi Peng,Yuan Cai,Wei Liu,Yuanliang Yan
出处
期刊:Cancers
[MDPI AG]
日期:2022-09-24
卷期号:14 (19): 4639-4639
被引量:8
标识
DOI:10.3390/cancers14194639
摘要
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 TGFβ-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-β1 signaling, and treating with TGF-β1 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-β1-mediated EMT affecting platinum sensitivity and immune response in OC patients.
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