Targeting GPX4 in human cancer: Implications of ferroptosis induction for tackling cancer resilience

Cancer Letters, Journal Year: 2023, Volume and Issue: 559, P. 216119 - 216119

Published: March 7, 2023

Language: Английский

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USP8 positively regulates hepatocellular carcinoma tumorigenesis and confers ferroptosis resistance through β-catenin stabilization

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(6)

Published: June 13, 2023

Abstract Hepatocellular carcinoma (HCC) is the most common type of primary hepatic carcinoma, which a growing public health problem worldwide. One main genetic alterations in HCC deregulated Wnt/β-catenin signaling, activation β-catenin associated with progression HCC. In present study, we aimed to identify novel modulators controlling ubiquitination and stability. USP8 was overexpressed tissues correlated protein level. High expression indicated poor prognosis patients. depletion significantly decreased level, target genes TOP-luciferase activity cells. Further mechanistic study revealed that USP domain interacted ARM β-catenin. stabilized via inhibiting K48-specific poly-ubiquitination process on protein. addition, inhibited proliferation, invasion stemness cells conferred ferroptosis resistance, effects could be further rescued by overexpression. inhibitor DUB-IN-3 aggressive phenotype promoted through degradation Thus, our demonstrated activated Wnt/beta-catenin signaling post-translational mechanism Targeting may serve as promising strategy for patients

Language: Английский

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LINC00942 inhibits ferroptosis and induces the immunosuppression of regulatory T cells by recruiting IGF2BP3/SLC7A11 in hepatocellular carcinoma

Functional & Integrative Genomics, Journal Year: 2024, Volume and Issue: 24(1)

Published: Feb. 1, 2024

Abstract Hepatocellular carcinoma (HCC) is a common malignant tumor with high recurrence rate and poor prognosis. Long intergenic nonprotein coding RNA 942 (LINC00942) reported to be related ferroptosis the immune response in HCC serves as an oncogene various cancers. This research aimed explore contribution of LINC00942 progression. Functional assays were used evaluate functional role vitro vivo. Mechanistic conducted assess association insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) solute carrier family 7 member 11 (SLC7A11) regulatory pattern cells. was found exhibit upregulation tissue facilitated cell proliferation, suppressed ferroptosis, converted naive CD4 + T cells inducible Treg (iTreg) by regulating SLC7A11. Furthermore, SLC7A11 expression positively modulated IGF2BP3 shared RNA-binding (RBP) for The between 3′ untranslated region verified, recruit promote stability m6A-dependent manner. Moreover, mouse proliferation inhibited, number FOXP3 CD25 increased, while enhanced after knockdown suppresses induces immunosuppression recruiting enhance stability, which may provide novel therapeutic targets HCC.

Language: Английский

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Non-Coding RNA: A Key Regulator in the Glutathione-GPX4 Pathway of Ferroptosis

Non-coding RNA Research, Journal Year: 2024, Volume and Issue: 9(4), P. 1222 - 1234

Published: May 20, 2024

Ferroptosis, a form of regulated cell death, has emerged as crucial process in diverse pathophysiological states, encompassing cancer, neurodegenerative ailments, and ischemia-reperfusion injury. The glutathione (GSH)-dependent lipid peroxidation pathway, chiefly governed by peroxidase 4 (GPX4), assumes an essential part driving ferroptosis. GPX4, the principal orchestrator ferroptosis, garnered significant attention across cardiovascular, neuroscience domains over past decade. Noteworthy investigations have elucidated indispensable functions ferroptosis numerous diseases, including tumorigenesis, wherein robust within cells can impede tumor advancement. Recent research underscored complex regulatory role non-coding RNAs (ncRNAs) regulating GSH-GPX4 network, thus influencing cellular susceptibility to This exhaustive review endeavors probe into multifaceted processes which ncRNAs control network Specifically, we delve miRNAs, lncRNAs, circRNAs GPX4 expression impacting Moreover, discuss clinical implications dysregulated interactions between several conditions, underscoring their capacity viable targets for therapeutic intervention. Additionally, explores emerging strategies aimed at targeting modulate pathway manipulate advantage. A comprehensive understanding these intricate networks furnishes insights innovative avenues diseases associated with perturbed thereby laying groundwork interventions ferroptosis-related pathological conditions.

Language: Английский

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Competing endogenous RNA networks and ferroptosis in cancer: novel therapeutic targets

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(5)

Published: May 22, 2024

Abstract As a newly identified regulated cell death, ferroptosis is metabolically driven process that relies on iron and associated with polyunsaturated fatty acyl peroxidation, elevated levels of reactive oxygen species (ROS), mitochondrial damage. This distinct death dysregulated in various cancers; activating malignant cells increases cancer immunotherapy chemoradiotherapy responses across different malignancies. Over the last decade, accumulating research has provided evidence cross-talk between non-coding RNAs (ncRNAs) competing endogenous RNA (ceRNA) networks highlighted their significance developing progressing Aside from pharmaceutical agents to regulate ferroptosis, recent studies have shed light potential restoring ferroptosis-related ceRNA treatment. The present study provides comprehensive up-to-date review significance, pathways, role chemoradiotherapy, biogenesis, ferroptosis-regulating cancers. insights can offer authorship state-of-the-art findings future perspectives regarding implication treatment determining prognosis affected patients.

Language: Английский

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The Regulation of Ferroptosis by Noncoding RNAs

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13336 - 13336

Published: Aug. 28, 2023

As a novel form of regulated cell death, ferroptosis is characterized by intracellular iron and lipid peroxide accumulation, which different from other death forms morphologically, biochemically, immunologically. Ferroptosis metabolism, antioxidant defense systems as well various transcription factors related signal pathways. Emerging evidence has highlighted that associated with many physiological pathological processes, including cancer, neurodegeneration diseases, cardiovascular ischemia/reperfusion injury. Noncoding RNAs are group functional RNA molecules not translated into proteins, can regulate gene expression in manners. An increasing number studies have shown noncoding RNAs, especially miRNAs, lncRNAs, circRNAs, interfere the progression modulating ferroptosis-related genes or proteins directly indirectly. In this review, we summarize basic mechanisms regulations focus on recent mechanism for types ncRNAs to conditions, will deepen our understanding regulation provide new insights employing ferroptosis-associated therapeutic strategies.

Language: Английский

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Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer’s disease

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(3), P. 613 - 631

Published: March 1, 2024

Alzheimer’s disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, cure for has not yet been found. Oxidative stress mediates excessive oxidative responses, its involvement in pathogenesis as primary or secondary pathological event widely accepted. As member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With discovery ferroptosis, central role anti-lipid peroxidation several diseases, including disease, received widespread attention. Increasing evidence suggests that expression inhibited brain, resulting stress, inflammation, apoptosis, which are closely associated damage disease. Several therapeutic approaches, such small molecule drugs, natural plant products, non-pharmacological treatments, ameliorate cognitive function by promoting enhancing activity. Therefore, upregulation may be promising strategy treatment This review provides overview gene structure, biological functions, regulatory mechanisms 4, discussion on important events related summary advances small-molecule therapies targeting Most prior studies this subject used animal models, relevant clinical lacking. Future trials required validate effects strategies

Language: Английский

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TMEM44-AS1 promotes esophageal squamous cell carcinoma progression by regulating the IGF2BP2-GPX4 axis in modulating ferroptosis

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Dec. 1, 2023

The long non-coding RNA (lncRNA) TMEM44-AS1 is a novel lncRNA whose pro-carcinogenic role in gastric cancer and glioma has been demonstrated. However, its function esophageal squamous cell carcinoma (ESCC) unknown. In this study, we identified that was highly expressed ESCC tissues cells. Functionally, promoted proliferation, invasion metastasis vitro vivo. inhibited ferroptosis cells, levels were significantly increased after knockdown of TMEM44-AS1. Mechanistically, positively correlated with GPX4 expression, could bind to the RNA-binding protein IGF2BP2 enhance stability mRNA, thereby affecting regulating malignant progression ESCC. summary, study reveals TMEM44-AS1-IGF2BP2-GPX4 axis influence can be used as potential treatment target against

Language: Английский

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FOXP3 promote the progression of glioblastoma via inhibiting ferroptosis mediated by linc00857/miR-1290/GPX4 axis

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(4)

Published: April 1, 2024

The oncogenic properties of members belonging to the forkhead box (FOX) family have been extensively documented in different types cancers. In this study, our objective was investigate impact FOXP3 on glioblastoma multiforme (GBM) cells. By conducting a screen using small hairpin RNA (shRNA) library, we discovered significant association between and ferroptosis GBM Furthermore, observed elevated levels both tissues cell lines, which correlated with poorer prognosis. found promote proliferation cells by inhibiting vitro vivo. Mechanistically, not only directly upregulated transcription GPX4, but also attenuated degradation GPX4 mRNA through linc00857/miR-1290 axis, thereby suppressing promoting proliferation. Additionally, inhibitor epirubicin exhibited ability impede induce summary, study provided evidences that facilitates progression via linc00857/miR-1290/GPX4 highlighting as potential therapeutic target for GBM.

Language: Английский

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Current knowledge of ferroptosis in the pathogenesis and prognosis of oral squamous cell carcinoma

Cellular Signalling, Journal Year: 2024, Volume and Issue: 119, P. 111176 - 111176

Published: April 16, 2024

Language: Английский

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