Ferritin in glioblastoma

Jaksch-Bogensperger, Heidi; Spiegl-Kreinecker, Sabine; Arosio, Paolo; Eckl, Peter; Golaszewski, Stefan; Ebner, Yvonne; Al-Schameri, Rahman; Strasser, Peter; Weis, Serge; Bresgen, Nikolaus

doi:10.1038/s41416-020-0808-8

Cited by 15 publications

(10 citation statements)

References 16 publications

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“…Ferritin, composed of ferritin heavy chain (FTH1) and ferritin light chain (FTL), is an iron storage protein in cells. Recent findings strongly support the hypothesis that glial tumors synthesize and secrete ferritin ( 26 , 27 ). Iron requirements are increased in glioblastoma stem cells, so high levels of cytoplasmic ferritin may protect cells from ferroptosis by enhancing iron chelation ( 28 ).…”

Section: Regulation Of Ferroptosis In Gliomasupporting

confidence: 66%

“…The higher the grade of glioma, the correspondingly stronger the treatment resistance effect it has. Purified ferritin from glioblastoma-derived cell line has marked apoptosis-stimulating activity and are inhibited by neutralizing anti-ferritin antibody Ab rH02, however, isoferrin released from cultured neonatal astrocytes did not show this activity, suggesting that the transition of astrocytes to a malignant phenotype is accompanied by alterations in iron metabolic processes ( 26 ). And research demonstrated that the extent of TfR expression in glioma is positively correlated with tumor grading ( 29 ).…”

Section: Regulation Of Ferroptosis In Gliomamentioning

confidence: 99%

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Emerging roles of ferroptosis in glioma

et al. 2022

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Glioma is the most common primary malignant tumor in the central nervous system, and directly affects the quality of life and cognitive function of patients. Ferroptosis, is a new form of regulated cell death characterized by iron-dependent lipid peroxidation. Ferroptosis is mainly due to redox imbalance and involves multiple intracellular biology processes, such as iron metabolism, lipid metabolism, and antioxidants synthesis. Induction of ferroptosis could be a new target for glioma treatment, and ferroptosis-related processes are associated with chemoresistance and radioresistance in glioma. In the present review, we provide the characteristics, key regulators and pathways of ferroptosis and the crosstalk between ferroptosis and other programmed cell death in glioma, we also proposed the application and prospect of ferroptosis in the treatment of glioma.

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Section: Regulation Of Ferroptosis In Gliomasupporting

confidence: 66%

Section: Regulation Of Ferroptosis In Gliomamentioning

confidence: 99%

Emerging roles of ferroptosis in glioma

et al. 2022

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“…The association between high-grade glioma and iron metabolism has been reported previously. Jaksch-Bogensperger et al showed that patients with high-grade glioma have higher serum ferritin levels (12). Glioblastoma cancer stem-like cells can absorb iron from the microenvironment more effectively, by upregulating their expression levels of ferritin and transferrin receptor 1 (8).…”

Section: Introductionmentioning

confidence: 99%

Identification of Iron Metabolism-Related Genes as Prognostic Indicators for Lower-Grade Glioma

Wang

et al. 2021

Front. Oncol.

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Lower-grade glioma (LGG) is characterized by genetic and transcriptional heterogeneity, and a dismal prognosis. Iron metabolism is considered central for glioma tumorigenesis, tumor progression and tumor microenvironment, although key iron metabolism-related genes are unclear. Here we developed and validated an iron metabolism-related gene signature LGG prognosis. RNA-sequence and clinicopathological data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) were downloaded. Prognostic iron metabolism-related genes were screened and used to construct a risk-score model via differential gene expression analysis, univariate Cox analysis, and the Least Absolute Shrinkage and Selection Operator (LASSO)-regression algorithm. All LGG patients were stratified into high- and low-risk groups, based on the risk score. The prognostic significance of the risk-score model in the TCGA and CGGA cohorts was evaluated with Kaplan-Meier (KM) survival and receiver operating characteristic (ROC) curve analysis. Risk- score distributions in subgroups were stratified by age, gender, the World Health Organization (WHO) grade, isocitrate dehydrogenase 1 (IDH1) mutation status, the O6‐methylguanine‐DNA methyl‐transferase (MGMT) promoter-methylation status, and the 1p/19q co-deletion status. Furthermore, a nomogram model with a risk score was developed, and its predictive performance was validated with the TCGA and CGGA cohorts. Additionally, the gene set enrichment analysis (GSEA) identified signaling pathways and pathological processes enriched in the high-risk group. Finally, immune infiltration and immune checkpoint analysis were utilized to investigate the tumor microenvironment characteristics related to the risk score. We identified a prognostic 15-gene iron metabolism-related signature and constructed a risk-score model. High risk scores were associated with an age of > 40, wild-type IDH1, a WHO grade of III, an unmethylated MGMT promoter, and 1p/19q non-codeletion. ROC analysis indicated that the risk-score model accurately predicted 1-, 3-, and 5-year overall survival rates of LGG patients in the both TCGA and CGGA cohorts. KM analysis showed that the high-risk group had a much lower overall survival than the low-risk group (P < 0.0001). The nomogram model showed a strong ability to predict the overall survival of LGG patients in the TCGA and CGGA cohorts. GSEA analysis indicated that inflammatory responses, tumor-associated pathways, and pathological processes were enriched in high-risk group. Moreover, a high risk score correlated with the infiltration immune cells (dendritic cells, macrophages, CD4+ T cells, and B cells) and expression of immune checkpoint (PD1, PDL1, TIM3, and CD48). Our prognostic model was based on iron metabolism-related genes in LGG, can potentially aid in LGG prognosis, and provides potential targets against gliomas.

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“…Ferritin is an iron storage protein whose level reflects the iron reserve and iron load in the body (Golan et al, 2021). It is elevated during infectious diseases, tumors and inflammation (Jaksch-Bogensperger et al, 2020;Kim et al, 2013). Studies have shown that iron at high concentration could accelerate the formation of free radicals and oxidation of atherogenic lipoproteins such as cholesterol (Cozzi et al, 1990;Ikeda et al, 2006;Tuomainen et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Silencing ferritin alleviates atherosclerosis in mice via regulating the expression levels of matrix metalloproteinases and interleukins

Zheng

Liu

et al. 2021

Acta Biochim Pol

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This study was conducted to investigate the roles of ferritin in atherosclerosis. The mouse model of atherosclerosis was established by feeding ApoE knockout mice with a high-fat diet. The mice were then treated with ferritin-overexpressing and -silencing constructs, and assessed for interleukins (ILs) and matrix metalloproteinases (MMPs) levels using ELISA and Western blot analysis. After being fed with a high-fat diet, the ApoE knockout mice developed pro-atherogenic lipid profiles with elevated total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C). They also showed increased atherosclerotic lesions including narrowed lumen diameter, reduced lumen area, and increased plaque size. Following injection of the overexpression and silencing constructs, mRNA levels of ferritin were increased and decreased, respectively, and at the same time the atherosclerotic lesions were aggravated and alleviated, respectively. Further analysis indicated that silencing of ferritin gene reduced IL-1β and IL-10 levels while overexpressing ferritin increased them. On other hand, the TNF-α levels showed an opposite trend. MMP8, MMP12 and MMP13 levels were increased or decreased significantly after the mice were injected with ferritin over-expression or silencing vectors, respectively. Western blot analysis showed that compared to the control, overexpressing ferritin resulted in increased expression of p-JNK while silencing ferritin decreased the expression. Meanwhile, the levels of pc-Jun remained unchanged. Our work demonstrates that ferritin can regulate the progress of atherosclerosis via regulating the expression levels of MMPs and interleukins. Silencing ferritin inhibits the development of atherosclerosis and is, therefore, worth being further investigated as a potential therapeutic approach for this disease.

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Ferritin in glioblastoma

Cited by 15 publications

References 16 publications

Emerging roles of ferroptosis in glioma

Emerging roles of ferroptosis in glioma

Identification of Iron Metabolism-Related Genes as Prognostic Indicators for Lower-Grade Glioma

Silencing ferritin alleviates atherosclerosis in mice via regulating the expression levels of matrix metalloproteinases and interleukins

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