GSK-3β manipulates ferroptosis sensitivity by dominating iron homeostasis

Wang, Lingjuan; Ouyang, Sijin; Li, Bin; Wu, Hao; Wang, Fengli

doi:10.1038/s41420-021-00726-3

Cited by 24 publications

(17 citation statements)

References 51 publications

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“…In mammals, TFR1 imports the transferrin-bound iron from the extracellular environment into cells. Interestingly, the intracellular labile free iron is indispensable for lipid peroxidation and ferroptosis execution 54 . On the other hand, protein phosphatase 1 regulatory inhibitor subunit 1b ( PPP1R1B ) was positively associated with MUFA traits but negatively correlated with PUFA traits (Fig.…”

Section: Discussionmentioning

confidence: 99%

Global analysis of the association between pig muscle fatty acid composition and gene expression using RNA-Seq

Valdés-Hernández

Ramayo-Caldas

Passols

et al. 2023

Sci Rep

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Fatty acids (FAs) play an essential role as mediators of cell signaling and signal transduction, affecting metabolic homeostasis and determining meat quality in pigs. However, FAs are transformed by the action of several genes, such as those encoding desaturases and elongases of FAs in lipogenic tissues. The aim of the current work was to identify candidate genes, biological processes, and pathways involved in the modulation of intramuscular FA profile from longissimus dorsi muscle. FA profile by gas chromatography of methyl esters and gene expression by RNA-Seq were determined in 129 Iberian × Duroc backcrossed pigs. An association analysis between the muscle transcriptome and its FA profile was performed, followed by a concordance and functional analysis. Overall, a list of well-known (e.g., PLIN1, LEP, ELOVL6, SC5D, NCOA2, ACSL1, MDH1, LPL, LGALS12, TFRC, GOT1, and FBP1) and novel (e.g., TRARG1, TANK, ENSSSCG00000011196, and ENSSSCG00000038429) candidate genes was identified, either in association with specific or several FA traits. Likewise, several of these genes belong to biological processes and pathways linked to energy, lipid, and carbohydrate metabolism, which seem determinants in the modulation of FA compositions. This study can contribute to elucidate the complex relationship between gene expression and FA profile in pig muscle.

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Section: Discussionmentioning

confidence: 99%

Global analysis of the association between pig muscle fatty acid composition and gene expression using RNA-Seq

Valdés-Hernández

Ramayo-Caldas

Passols

et al. 2023

Sci Rep

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“…It has been reported that FTL plays a role in the process of apoptosis ( Fan et al, 2009 ), but more studies regard FTL as a factor related to iron metabolism and consider it to play a role in ferroptosis. Gsk-3β affects ferroptosis by antagonizing iron metabolites, including FTL, and disrupting iron homeostasis ( Wang et al, 2021a ). Transcriptional inhibition of FTL has also been reported to increase the sensitivity of cancer cells to ferroptosis in lung adenocarcinoma ( Wang et al, 2021b ).…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis Reveals Critical Ferroptosis Regulators and FTL Contribute to Cancer Progression in Hepatocellular Carcinoma

Wang

et al. 2022

Front. Genet.

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Background: The carcinogenesis and prognosis of hepatocellular carcinoma (HCC) involve complex molecular mechanisms, and ferroptosis is related to the development and therapeutic efficacy of HCC, but the specific mechanism and prognostic role of ferroptosis-related genes in HCC have not been elucidated.Methods: Differentially expressed gene analysis, Cox regression, and unsupervised consensus clustering were applied to identify crucial ferroptosis regulators and establish ferroptosis-related subtypes in HCC. Random forest analysis and survival analysis were adopted to confirm FTL as the hub prognostic and diagnostic ferroptosis regulator in HCC.Results: The ferroptosis-related subtypes based on the crucial prognostic ferroptosis regulators showed that patients in fescluster A had a higher survival probability (p < 0.001) and better clinical characteristics than patients in fescluster B in the TCGA-LIHC cohort. Patients with a high tumor mutation burden (TMB) in fescluster B presented a significantly poorer prognosis. FTL was the core ferroptosis regulator, and its low expression revealed a significant survival advantage compared with its high expression (p = 0.03). The expression and predictive value of FTL were both closely related to the clinical features (p < 0.05). Expression of FTL accurately distinguished HCC from normal tissues in the TCGA-LIHC cohort, ICGC cohort, and GSE14520 dataset. In addition, higher infiltrating fractions of immune cells, such as activated CD8+ T cells and Gamma delta T cells, mainly enriched immune-related signaling pathways, including the IL2-STAT3 signaling pathway and interferon-gamma response signaling pathway, and higher expression of immune checkpoints, including PDCD1, CTLA4, TIGIT, and CD83, were presented in patients with high FTL expression (p < 0.05). Patients with high FTL were more sensitive to some targeted drugs, such as cisplatin, dasatinib, and sorafenib, than those with low FTL (p < 0.05). A nomogram based on FTL accurately predicted the prognosis of HCC. Further knockdown of FTL was determined to significantly inhibit cell proliferation and migration in HCC.Conclusion: Our study validated ferroptosis-related subtypes and FTL with effective prognostic value in HCC and was beneficial for identifying candidates suitable for targeted drug therapy and immunotherapy, thereby offering further insight into individual treatment strategies to improve disease outcomes in HCC patients.

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“…A number of malignancies, including lung cancer (40), esophageal cancer (41), and HCC (42) have been linked to TXNRD1, and this gene has been proven to have a role (42). Histological examination of hepatocellular cancer specimens revealed high levels of FTL expression (44), and it figured prominently in HCC apoptosis and iron metabolism (45,46). The selenoenzyme glutathione peroxidase (GPX4) has been identified through genetic investigations in cells and animals as a crucial regulator of ferroptosis (47).…”

Section: Discussionmentioning

confidence: 99%

Ferroptosis and cuproptosis prognostic signature for prediction of prognosis, immunotherapy and drug sensitivity in hepatocellular carcinoma: development and validation based on TCGA and ICGC databases

Ma¹,

Hui²,

Huang³

et al. 2023

Transl Cancer Res

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Background: Hepatocellular carcinoma (HCC) is a common malignancy. Ferroptosis and cuproptosis promote HCC spread and proliferation. While fewer studies have combined ferroptosis and cuproptosis to construct prognostic signature of HCC. This work attempts to establish a novel scoring system for predicting HCC prognosis, immunotherapy, and medication sensitivity based on ferroptosis-related genes (FRGs) and cuproptosis-related genes (CRGs). Methods: FerrDb and previous literature were used to identify FRGs. CRGs came from original research. The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases included the HCC transcriptional profile and clinical information [survival time, survival status, age, gender, Tumor Node Metastasis (TNM) stage, etc.]. Correlation, Cox, and least absolute shrinkage and selection operator (LASSO) regression analyses were used to narrow down prognostic genes and develop an HCC risk model. Using "caret", R separated TCGA-HCC samples into a training risk set and an internal test risk set.As external validation, we used ICGC samples. We employed Kaplan-Meier analysis and receiver operating characteristic (ROC) curve to evaluate the model's clinical efficacy. CIBERSORT and TIMER measured immunocytic infiltration in high-and low-risk populations.

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GSK-3β manipulates ferroptosis sensitivity by dominating iron homeostasis

Cited by 24 publications

References 51 publications

Global analysis of the association between pig muscle fatty acid composition and gene expression using RNA-Seq

Global analysis of the association between pig muscle fatty acid composition and gene expression using RNA-Seq

Integrated Analysis Reveals Critical Ferroptosis Regulators and FTL Contribute to Cancer Progression in Hepatocellular Carcinoma

Ferroptosis and cuproptosis prognostic signature for prediction of prognosis, immunotherapy and drug sensitivity in hepatocellular carcinoma: development and validation based on TCGA and ICGC databases

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