[Ferroptosis suppressor genes are highly expressed in esophageal cancer to inhibit tumor cell ferroptosis].
Nan Fang Yi Ke Da Xue Xue Bao
; 44(7): 1389-1396, 2024 Jul 20.
Article
en Zh
| MEDLINE
| ID: mdl-39051085
ABSTRACT
OBJECTIVE:
To explore the role of ferroptosis-related genes in regulating ferroptosis of esophageal squamous cell carcinoma (ESCC).METHODS:
ESCC datasets GSE161533 and GSE20347 were downloaded from the Gene Expression Omnibus (GEO) to identify the differentially expressed genes (DEGs) using R software. ESCC ferroptosis-related genes obtained by intersecting the DEGs with ferroptosis-related genes from FerrDb were analyzed using GO and KEGG analyses, protein-protein interaction (PPI) network analysis, and core gene identification through Cytoscape. The identified ferroptosis suppressor genes were validated using TCGA database, and their expression levels were detected using RT-qPCR in cultured normal esophageal cells and ESCC cells. Six ferroptosis suppressor genes (RRM2, GCLC, TFRC, TXN, SLC7A11, and EZH2) were downregulated with siRNA in ESCC cells, and the changes in cell proliferation and apoptosis were assessed with CCK8 assay and flow cytometry; Western blotting was performed to examine the changes in ferroptosis progression of the cells.RESULTS:
We identified a total of 58 ESCC ferroptosis-related genes, which involved such biological processes as glutathione transmembrane transport, iron ion transport, and apoptosis and the ferroptosis, glutathione metabolism, and antifolate resistance pathways. The PPI network included 54 nodes and 74 edges with a clustering coefficient of 0.522 and PPI enrichment P<0.001. Cytoscape identified 6 core ferroptosis suppressor genes (RRM2, TFRC, TXN, EZH2, SLC7A11, and GCLC), which were highly expressed in ESCC tissues in the TCGA dataset and in ESCC cell lines. Downregulating these genes in ESCC TE1 cells significantly inhibited cell proliferation, promoted cell apoptosis, reduced the expression levels of ferroptosis markers GPX4 and FIH1, and increased the expression of ACSL4.CONCLUSION:
High expression of ferroptosis suppressor genes in ESCC may cause arrest of ferroptosis progression to facilitate tumor development, and inhibiting these genes can restore ferroptosis and promote cell apoptosis, suggesting their value as potential therapeutic targets for ESCC.Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Neoplasias Esofágicas
/
Apoptosis
/
Proliferación Celular
/
Carcinoma de Células Escamosas de Esófago
/
Ferroptosis
Límite:
Humans
Idioma:
Zh
Revista:
Nan Fang Yi Ke Da Xue Xue Bao
/
Nanfang Yike Daxue xuebao
Año:
2024
Tipo del documento:
Article
País de afiliación:
China