Regulation of GSK3β/Nrf2 signaling pathway modulated erastin-induced ferroptosis in breast cancer

Wu, Xinghan; Liu, Chuanliang; Li, Zihaoran; Gai, Chengcheng; Ding, Dejun; Chen, Weijuan; Hao, Fengyun; Li, Wentong

doi:10.1007/s11010-020-03821-8

Cited by 64 publications

(39 citation statements)

References 28 publications

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“…In addition, Dihydroisonone I (DT), a pure compound present in Salvia miltiorrhiza, can inhibit GPX4 protein expression and induce ferroptosis through lipid peroxidation to improve the prognosis of breast cancer [ 9 ]. In terms of mechanism, elastin induces ferroptosis in breast cancer via the Glycogen synthase kinase-3β (GSK3β) / (nuclear factor erythroid 2-related factor 2) Nrf2 signaling pathway [ 10 ]. Besides, acyl-CoA synthetase long-chain family member 4 (ACSL4) can increase the content of intracellular lipids to promote ferroptosis [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of the prognostic value of ferroptosis-related gene signature in breast cancer patients

Wang

Wei

et al. 2021

BMC Cancer

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Background Breast cancer (BRCA) is a malignant tumor with high morbidity and mortality, which is a threat to women’s health worldwide. Ferroptosis is closely related to the occurrence and development of breast cancer. Here, we aimed to establish a ferroptosis-related prognostic gene signature for predicting patients’ survival. Methods Gene expression profile and corresponding clinical information of patients from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. The Least absolute shrinkage and selection operator (LASSO)-penalized Cox regression analysis model was utilized to construct a multigene signature. The Kaplan-Meier (K-M) and Receiver Operating Characteristic (ROC) curves were plotted to validate the predictive effect of the prognostic signature. Gene Ontology (GO) and Kyoto Encyclopedia of Genes, Genomes (KEGG) pathway and single-sample gene set enrichment analysis (ssGSEA) were performed for patients between the high-risk and low-risk groups divided by the median value of risk score. Results We constructed a prognostic signature consisted of nine ferroptosis-related genes (ALOX15, CISD1, CS, GCLC, GPX4, SLC7A11, EMC2, G6PD and ACSF2). The Kaplan-Meier curves validated the fine predictive accuracy of the prognostic signature (p < 0.001). The area under the curve (AUC) of the ROC curves manifested that the ferroptosis-related signature had moderate predictive power. GO and KEGG functional analysis revealed that immune-related responses were largely enriched, and immune cells, including activated dendritic cells (aDCs), dendritic cells (DCs), T-helper 1 (Th1), were higher in high-risk groups (p < 0.001). Oppositely, type I IFN response and type II IFN response were lower in high-risk groups (p < 0.001). Conclusion Our study indicated that the ferroptosis-related prognostic signature gene could serve as a novel biomarker for predicting breast cancer patients’ prognosis. Furthermore, we found that immunotherapy might play a vital role in therapeutic schedule based on the level and difference of immune-related cells and pathways in different risk groups for breast cancer patients.

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Section: Introductionmentioning

confidence: 99%

Identification of the prognostic value of ferroptosis-related gene signature in breast cancer patients

Wang

Wei

et al. 2021

BMC Cancer

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“…Recent research has found that prominin2 (PROM2) could reduce the ferroptosis of breast cancer cells and promote tumor progression by stimulating iron export ( Brown et al, 2019 ). Additionally, another study has reported that GSK3β/Nrf2 signaling pathway was activated in breast cancer, increasing the expression level of Nrf2 to resist ferroptosis ( Wu et al, 2020 ). These studies suggest that resistance of ferroptosis is important for the progression of breast cancer.…”

Section: Introductionmentioning

confidence: 99%

A Ferroptosis-Related lncRNAs Signature Predicts Prognosis and Immune Microenvironment for Breast Cancer

Zhang

Ping

et al. 2021

Front. Mol. Biosci.

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Background: Ferroptosis, a regulated cell death which is driven by the iron-dependent peroxidation of lipids, plays an important role in cancer. However, studies about ferroptosis-related Long non-coding RNAs (lncRNAs) in breast cancer (BC) are limited. Besides, the prognostic role of ferroptosis-related lncRNAs and their relationship to immune microenvironment in breast cancer remain unclear. This study aimed to explore the potential prognostic value of ferroptosis-related lncRNAs and their relationship to immune microenvironment in breast cancer.Methods: RNA-sequencing data of female breast cancer patients were downloaded from TCGA database. 937 patients were randomly separated into training or validation cohort in 2:1 ratio. Ferroptosis-related lncRNAs were screened by Pearson correlation analysis with 239 reported ferroptosis-related genes. A ferroptosis-related lncRNAs signature was constructed with univariate and multivariate Cox regression analyses in the training cohort, and its prognostic value was further tested in the validation cohort.Results: An 8-ferroptosis-related-lncRNAs signature was developed by multivariate Cox regression analysis to divide patients into two risk groups. Patients in the high-risk group had worse prognosis than patients in the low-risk group. Multivariate Cox regression analysis showed the risk score was an independent prognostic indicator. Receiver operating characteristic curve (ROC) analysis proved the predictive accuracy of the signature. The area under time-dependent ROC curve (AUC) reached 0.853 at 1 year, 0.802 at 2 years, 0.740 at 5 years in the training cohort and 0.791 at 1 year, 0.778 at 2 years, 0.722 at 5 years in the validation cohort. Further analysis demonstrated that immune-related pathways were significantly enriched in the high-risk group. Analysis of the immune cell infiltration landscape showed that breast cancer in the high-risk group tended be immunologically “cold”.Conclusion: We identified a novel ferroptosis-related lncRNA signature which could precisely predict the prognosis of breast cancer patients. Ferroptosis-related lncRNAs may have a potential role in the process of anti-tumor immunity and serve as therapeutic targets for breast cancer.

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“…However, melatonin inhibits the ferroptosis of neurons through the AKT/NRF2/GPX4 signaling pathway, thereby promoting the survival of hippocampus neurons and improving the hypoxicischemic brain injury (Gou et al, 2020). Meanwhile, GPX4 regulates erastin-induced ferroptosis via the GSK3/NRF2/GPX4 signaling pathway in breast cancer (Wu et al, 2020). Bilirubin chelates iron, while significantly increasing the expression of GPX4, upregulating NRF2/HO-1, and reducing ferroptosis in islet cells (Yao et al, 2020).…”

Section: Gpx4 and Ferroptosismentioning

confidence: 99%

“…FSP1 catalyzes the regeneration of CoQ10 through NADPH (Doll et al, 2019). CoQ10, as a part of the mitochondrial electron chain, not only participates in electron transport in the respiratory chain but also inhibits Sun et al, 2016;Fan et al, 2017;Dodson et al, 2019;Dong et al, 2020;Gou et al, 2020;Wu et al, 2020;Yao et al, 2020;Zhou, 2020 Iron chaperone PCBP1 Iron chaperone PCBP1 can limit the toxicity of intracellular iron and prevent Ferroptosis caused by lipid peroxidation CCA CCA inhibited ferroptosis by activation of system X c − /GPX4/Nrf2 and inhibition of NCOA4.…”

Section: Gpx4 and Ferroptosismentioning

confidence: 99%

Iron Metabolism and Ferroptosis in Epilepsy

Chen

Zhang

et al. 2020

Front. Neurosci.

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Epilepsy is a disease characterized by recurrent, episodic, and transient central nervous system (CNS) dysfunction resulting from an excessive synchronous discharge of brain neurons. It is characterized by diverse etiology, complex pathogenesis, and difficult treatment. In addition, most epileptic patients exhibit social cognitive impairment and psychological impairment. Iron is an essential trace element for human growth and development and is also involved in a variety of redox reactions in organisms. However, abnormal iron metabolism is associated with several neurological disorders, including hemorrhagic post-stroke epilepsy and post-traumatic epilepsy (PTE). Moreover, ferroptosis is also considered a new form of regulation of cell death, which is attributed to severe lipid peroxidation caused by the production of reactive oxygen species (ROS) and iron overload found in various neurological diseases, including epilepsy. Therefore, this review summarizes the study on iron metabolism and ferroptosis in epilepsy, in order to elucidate the correlation between iron and epilepsy. It also provides a novel method for the treatment, prevention, and research of epilepsy, to control epileptic seizures and reduce nerve injury after the epileptic seizure.

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Regulation of GSK3β/Nrf2 signaling pathway modulated erastin-induced ferroptosis in breast cancer

Cited by 64 publications

References 28 publications

Identification of the prognostic value of ferroptosis-related gene signature in breast cancer patients

Identification of the prognostic value of ferroptosis-related gene signature in breast cancer patients

A Ferroptosis-Related lncRNAs Signature Predicts Prognosis and Immune Microenvironment for Breast Cancer

Iron Metabolism and Ferroptosis in Epilepsy

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