Characterization of the functional effects of ferredoxin 1 as a cuproptosis biomarker in cancer

Li, Xiang; Dai, Zihan; Liu, Jincheng; Sun, Zhenqian; Li, Na; Jiao, Guangjun; Cao, Hongxin

doi:10.3389/fgene.2022.969856

Cited by 10 publications

(6 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We used the GEPIA, TIMER and BioGPS databases to analyze the levels of FDX1 expression in cancers and normal tissues as a first step in our study. In line with previous studies, the expression of FDX1 was significantly lower in most cancer types, except GBM, STAD, DLBC and THYM [10][11][12][13][14] . According to these results, FDX1 may play a role in oncogenesis and the progression of tumors.…”

Section: Discussionsupporting

confidence: 91%

“…Although previous bioinformatics analyses have proposed the potential value of FDX1 in cancer diagnosis and treatment, most studies lack external validation or are only validated across tumor cell lines 11 – 14 . In the present study, we conducted a comprehensive analysis to examine the role of FDX1 in human cancer prognosis and immunology.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prognostic and immunological role of FDX1 in pan-cancer: an in-silico analysis

Liu

Miao

2023

Sci Rep

View full text Add to dashboard Cite

Previous research has demonstrated that ferredoxin 1 (FDX1) contributes to the accumulation of toxic lipoylated dihydrolipoamide S-acetyltransferase (DLAT) and results in cuproptotic cell death. However, the role that FDX1 plays in human cancer prognosis and immunology is still not well understood. The original data was obtained from TCGA and GEO databases and integrated using R 4.1.0. The TIMER2.0, GEPIA, and BioGPS databases were used to explore FDX1 expression. The impact of FDX1 on prognosis was analyzed using the GEPIA and Kaplan–Meier Plotter databases. External validation will be performed using the PrognoScan database. FDX1 expression in different immune and molecular subtypes of human cancers was evaluated using the TISIDB database. The correlation between FDX1 expression and immune checkpoints (ICP), microsatellite instability (MSI), and tumor mutational burden (TMB) in human cancers was analyzed using R 4.1.0. The TIMER2.0 and GEPIA databases were used to study the relationship between FDX1 expression and tumor-infiltrating immune cells. With the c-BioPortal database, we investigated the genomic alterations of FDX1. Pathway analysis and assessment of the sensitivity potential of FDX1-related drugs were also performed. Using the UALCAN database, we analyzed the differential expression of FDX1 in KIRC (kidney renal clear cell carcinoma) with different clinical features. Coexpression networks of FDX1 were analyzed using LinkedOmics. In general, FDX1 was expressed differently in different types of cancer in humans. Expression of FDX1 was strongly correlated with patient prognosis, ICP, MSI, and TMB. FDX1 was also participated in immune regulation and the tumor microenvironment. Coexpression networks of FDX1 were primarily involved in oxidative phosphorylation regulation. Pathway analysis revealed that the expression of FDX1 was correlated to cancer-related and immune-related pathways. FDX1 has the potential to serve as a biomarker for pan-cancer prognosis and immunology, as well as a novel target for tumor therapy.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Prognostic and immunological role of FDX1 in pan-cancer: an in-silico analysis

Liu

Miao

2023

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Cu 2+ binds to lipoylated proteins engaged in the tricarboxylic acid (TCA) cycle of mitochondrial respiration ( 11 ). This interaction triggers the oligomerization of lipoylated proteins, subsequently resulting in the downregulation of Fe-S cluster protein expression ( 12 – 14 ), which in turn induces protein toxic stress and ultimately leads to cell death ( 5 ). Notably, FDX1 plays a multifaceted role in this mechanism.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive bioinformatics analysis reveals the role of cuproptosis-related gene Ube2d3 in myocardial infarction

Yang,

Wang,

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

BackgroundMyocardial infarction (MI) caused by severe coronary artery disease has high incidence and mortality rates, making its prevention and treatment a central and challenging aspect of clinical work for cardiovascular practitioners. Recently, researchers have turned their attention to a novel mechanism of cell death caused by Cu2+, cuproptosis.MethodsThis study integrated data from three MI-related bulk datasets downloaded from the Gene Expression Omnibus (GEO) database, and identified 16 differentially expressed genes (DEGs) related to cuproptosis by taking intersection of the 6378 DEGs obtained by differential analysis with 49 cuproptosis-related genes. Four hub genes, Dbt, Dlat, Ube2d1 and Ube2d3, were screened out through random forest analysis and Lasso analysis. In the disease group, Dbt, Dlat, and Ube2d1 showed low expression, while Ube2d3 exhibited high expression.ResultsFocusing on Ube2d3 for subsequent functional studies, we confirmed its high expression in the MI group through qRT-PCR and Western Blot detection after successful construction of a MI mouse model by left anterior descending (LAD) coronary artery ligation, and further clarified the correlation of cuproptosis with MI development by detecting the levels of cuproptosis-related proteins. Moreover, through in vitro experiments, Ube2d3 was confirmed to be highly expressed in oxygen-glucose deprivation (OGD)-treated cardiomyocytes AC16. In order to further clarify the role of Ube2d3, we knocked down Ube2d3 expression in OGD-treated AC16 cells, and confirmed Ube2d3’s promoting role in the hypoxia damage of AC16 cells by inducing cuproptosis, as evidenced by the detection of MTT, TUNEL, LDH release and cuproptosis-related proteins.ConclusionIn summary, our findings indicate that Ube2d3 regulates cuproptosis to affect the progression of MI.

show abstract

“…FDX1 expression is closely related to tumor biological behavior. Research shows that deep deletions and ampli cation of FDX1 gene, of which the main type of amino acid alteration is missense mutations, results in the genomic instability 17 . Patients with FDX1 genomic instability have lower survival rates.…”

Section: Discussionmentioning

confidence: 99%

Down-regulated FDX1 inhibited the proliferation and migration of renal cell carcinoma cells

Bai,

Wang,

Zhang

et al. 2023

Preprint

View full text Add to dashboard Cite

Background With the intensive study of cell death, a copper-related cell death mechanism has been uncovered that is different from other forms of cell death, which researchers have named cuproptosis. Ferredoxin1 (FDX1) is a key gene in cuproptosis. Available studies have shown that FDX1 expression is down-regulated in a variety of solid tumors and plays an inhibitory role in tumors. However, studies related to the role of FDX1 in renal cell carcinoma (RCC) and its mechanism are scarce and still need to be further explored. Methods Expression spectrum and clinical data obtained from TCGA were used to analyze the differential expression of FDX1 in various types of tumors, the relationship between FDX1 and different clinical features as well as patient survival and prognosis. Immunohistochemical staining experiments were used to verify the difference in FDX1 expression between RCC tissues and normal tissues. RT-qPCR and western blot were carried out to validate the expression of FDX1 between normal renal tubular epithelial cells and RCC cells at the mRNA and protein levels. The effects of FDX1 on the proliferation and migration ability of RCC cells were explored by CCK-8 and scratch assays. Finally, potential signaling pathways involved in FDX1 in RCC were analyzed via Gene Set Enrichment Analysis (GSEA)and subsequently validated using RT-qPCR. Results We found that FDX1 was lowly expressed in RCC tissues and cells, suggesting that FDX1 acts as a protective factor in RCC and that increased expression of FDX1 is favorable to the prognosis of patients. Tumor proliferation and invasive ability were inhibited after the expression of FDX1. In addition, GSEA analysis was significantly enriched in multiple signaling pathways including oxidative phosphorylation. RT-qPCR results indicated that the expression of some important genes in the oxidative phosphorylation pathway was also up-regulated after overexpression of FDX1 in RCC cells. Conclusion Low expression of FDX1 in RCC is associated with poor patient survival. Overexpression of FDX1 may be involved in inhibiting the proliferation and migration of RCC cells through the oxidative phosphorylation pathway.

show abstract

Characterization of the functional effects of ferredoxin 1 as a cuproptosis biomarker in cancer

Cited by 10 publications

References 32 publications

Prognostic and immunological role of FDX1 in pan-cancer: an in-silico analysis

Prognostic and immunological role of FDX1 in pan-cancer: an in-silico analysis

Comprehensive bioinformatics analysis reveals the role of cuproptosis-related gene Ube2d3 in myocardial infarction

Down-regulated FDX1 inhibited the proliferation and migration of renal cell carcinoma cells

Contact Info

Product

Resources

About