FSP1: a key regulator of ferroptosis

Trends in Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(9), P. 753 - 764

Published: June 24, 2023

Ferroptosis suppressor protein 1 (FSP1) is one of the main regulatory molecules ferroptosis. FSP1 functions through FSP1-coenzyme Q10 (CoQ10)-NAD(P)H axis and vitamin K redox cycle. regulated by upstream factors, including transcription factors noncoding RNA (ncRNA), subject to epigenetic modifications, which affect progress FSP1-related diseases. closely associated with poor prognosis malignant tumors plays an important role in disease treatment. This review aims provide a comprehensive understanding ferroptosis regulation summarizing pathways, possible mechanisms involving FSP1, relationship between

Language: Английский

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Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 10, 2023

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt

Language: Английский

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Epigenetically silenced lncRNA SNAI3-AS1 promotes ferroptosis in glioma via perturbing the m6A-dependent recognition of Nrf2 mRNA mediated by SND1

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: May 19, 2023

Abstract Background Ferroptosis has been linked to tumor progression and resistance antineoplastic therapy. Long noncoding RNA (lncRNA) exerts a regulatory role in various biological processes of cells, while the function molecular mechanism lncRNA ferroptosis are yet be clarified glioma. Methods Both gain-of-function loss-of-function experiments were employed investigate effects SNAI3-AS1 on tumorigenesis susceptibility glioma vitro vivo. Bioinformatics analysis, Bisulfite sequencing PCR, pull-down, RIP, MeRIP dual-luciferase reporter assay performed explore low expression downstream Results We found that inducer erastin downregulates by increasing DNA methylation level promoter. functions as suppressor Importantly, enhances anti-tumor activity promoting both Mechanistically, competitively binds SND1 perturbs m 6 A-dependent recognition Nrf2 mRNA 3’UTR SND1, thereby reducing stability Nrf2. Rescue confirmed overexpression silence can rescue gain- ferroptotic phenotypes SNAI3-AS1, respectively. Conclusions Our findings elucidate effect detailed SNAI3-AS1/SND1/Nrf2 signalling axis ferroptosis, provide theoretical support for inducing improve treatment.

Language: Английский

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Sonodynamic therapy and magnetic resonance-guided focused ultrasound: new therapeutic strategy in glioblastoma

Journal of Neuro-Oncology, Journal Year: 2023, Volume and Issue: 163(1), P. 219 - 238

Published: May 1, 2023

Glioblastoma (GB) is one of the most aggressive and difficult-to-treat brain tumors, with a poor prognosis limited treatment options. In recent years, sonodynamic therapy (SDT) magnetic resonance focused ultrasound (MRgFUS) have emerged as promising approaches for GB. SDT uses waves in combination sonosensitizer to selectively damage cancer cells, while MRgFUS delivers high-intensity precisely target tumor tissue disrupt blood-brain barrier enhance drug delivery. this review, we explore potential novel therapeutic strategy We discuss principles SDT, its mechanisms action, preclinical clinical studies that investigated use Gliomas. also highlight challenges, limitations, future perspectives SDT. Overall, hold promise potentially complementary modalities Further research needed optimize their parameters determine safety efficacy humans, but selective targeted destruction makes them an exciting area investigation field therapy.

Language: Английский

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CircRNF10 triggers a positive feedback loop to facilitate progression of glioblastoma via redeploying the ferroptosis defense in GSCs

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: Sept. 19, 2023

Glioma exhibit heterogeneous susceptibility for targeted ferroptosis. How circRNAs alterations in glioma promote iron metabolism and ferroptosis defense remains unclarified.The highly enriched glioblastoma (GBM) were obtained through analysis of sequencing datasets. Quantitative real-time PCR (qRT-PCR) was used to determine the expression circRNF10 normal brain tissue. Both gain-of-function loss-of-function studies assess effects on using vitro vivo assays. The hypothesis that ZBTB48 promotes established bioinformatics functional RNA pull-down immunoprecipitation (RIP) assays performed examine interaction between target proteins including ZBTB48, MKRN3 IGF2BP3. posttranslational modification mechanism verified coimmunoprecipitation (co-IP) ubiquitination transcription activation HSPB1 IGF2BP3 by confirmed luciferase reporter gene chromatin (ChIP) stabilizing effect explored actinomycin D assay. Finally, a series experiments explore influences progression.A novel circular RNA, hsa_circ_0028912 (named circRNF10), which is significantly upregulated tissues correlated with patients' poor prognosis. Through integrated circRNA-proteins datasets results, we reveal as transcriptional factor binding circRNF10, notably promoting upregulation remodel facilitates launch circRNF10/ZBTB48/IGF2BP3 positive feedback loop GSCs. Additionally, can competitively bind block E3 ubiquitin ligase activity enhance expression. Consequently, circRNF10-overexpressed stem cells (GSCs) display lower Fe2+ accumulation, selectively priming tumors evading.Our research presents abnormal causing molecular metabolic change glioma, leverage discover therapeutically exploitable vulnerability

Language: Английский

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Regulated cell death in glioma: promising targets for natural small-molecule compounds

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 18, 2024

Gliomas are prevalent malignant tumors in adults, which can be categorized as either localized or diffuse gliomas. Glioblastoma is the most aggressive and deadliest form of glioma. Currently, there no complete cure, median survival time less than one year. The main mechanism regulated cell death involves organisms coordinating elimination damaged cells at risk tumor transformation hijacked by microorganisms for pathogen replication. This process includes apoptosis, necroptosis, autophagy, ferroptosis, pyroptosis, necrosis, parthanayosis, entosis, lysosome-dependent death, NETosis, oxiptosis, alkaliptosis, disulfidaptosis. goal clinical oncology to develop therapies that promote effective cancer regulating oncology. Recently, scientists have utilized pertinent regulatory factors natural small-molecule compounds induce treatment By analyzing PubMed Web Science databases, this paper reviews research progress on regulation role aim provide help glioblastoma.

Language: Английский

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Ferroptosis and hepatocellular carcinoma: the emerging role of lncRNAs

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 23, 2024

Hepatocellular carcinoma is the most common form of primary liver cancer and poses a significant challenge to medical community because its high mortality rate. In recent years, ferroptosis, unique cell death, has garnered widespread attention. Ferroptosis, which characterized by iron-dependent lipid peroxidation mitochondrial alterations, closely associated with pathological processes various diseases, including hepatocellular carcinoma. Long non-coding RNAs (lncRNAs), are type functional RNA, play crucial regulatory roles in variety biological processes. this manuscript, we review lncRNAs key aspects summarize research progress on ferroptosis-related

Language: Английский

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Ferroptosis: mechanisms and therapeutic targets

MedComm, Journal Year: 2024, Volume and Issue: 5(12)

Published: Nov. 20, 2024

Ferroptosis is a nonapoptotic form of cell death characterized by iron-dependent lipid peroxidation in membrane phospholipids. Since its identification 2012, extensive research has unveiled involvement the pathophysiology numerous diseases, including cancers, neurodegenerative disorders, organ injuries, infectious autoimmune conditions, metabolic and skin diseases. Oxidizable lipids, overload iron, compromised antioxidant systems are known as critical prerequisites for driving overwhelming peroxidation, ultimately leading to plasma rupture ferroptotic death. However, precise regulatory networks governing ferroptosis ferroptosis-targeted therapy these diseases remain largely undefined, hindering development pharmacological agonists antagonists. In this review, we first elucidate core mechanisms summarize epigenetic modifications (e.g., histone modifications, DNA methylation, noncoding RNAs, N6-methyladenosine modification) nonepigenetic genetic mutations, transcriptional regulation, posttranslational modifications). We then discuss association between disease pathogenesis explore therapeutic approaches targeting ferroptosis. also introduce potential clinical monitoring strategies Finally, put forward several unresolved issues which progress needed better understand hope review will offer promise application therapies context human health disease.

Language: Английский

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Dexmedetomidine Inhibits Ferroptosis to Alleviate Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury by Regulating the HDAC2/FPN Pathway

Cardiovascular Drugs and Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Language: Английский

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m6A-modified circSTX6 as a key regulator of cervical cancer malignancy via SPI1 and IL6/JAK2/STAT3 pathways

Oncogene, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

In recent years, circRNAs have garnered increasing attention for their role in cervical cancer. However, the functions of many newly identified remain unclear and require further exploration. this study, we investigated expression oncogenic potential novel circRNA circSTX6 Our findings revealed that is highly expressed cancer (CC) significantly associated with poor patient prognosis, promoting cell survival, proliferation, invasion, migration. Mechanistically, enhances stability transcription factor SPI1 by binding to it, thereby upregulating IL6 activating JAK2/STAT3 signaling pathway. Additionally, METTL3-mediated N6-methyladenosine (m6A) modification stabilizes through recognition YTHDC1, forming a positive feedback regulatory loop among METTL3, circSTX6, SPI1. These not only deepen our understanding biological mechanisms underlying CC but also highlight as target molecular therapies.

Language: Английский

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