FSP1: a key regulator of ferroptosis

Trends in Molecular Medicine, Год журнала: 2023, Номер 29(9), С. 753 - 764

Опубликована: Июнь 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

Язык: Английский

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

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Дек. 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

Язык: 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, Год журнала: 2023, Номер 42(1)

Опубликована: Май 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.

Язык: Английский

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

Journal of Neuro-Oncology, Год журнала: 2023, Номер 163(1), С. 219 - 238

Опубликована: Май 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.

Язык: 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, Год журнала: 2023, Номер 42(1)

Опубликована: Сен. 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

Язык: Английский

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

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Янв. 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.

Язык: Английский

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Ferroptosis: mechanisms and therapeutic targets

MedComm, Год журнала: 2024, Номер 5(12)

Опубликована: Ноя. 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.

Язык: Английский

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Physiological and pathological functions of circular RNAs in the nervous system

Neural Regeneration Research, Год журнала: 2023, Номер 19(2), С. 342 - 349

Опубликована: Июль 7, 2023

Abstract Circular RNAs (circRNAs) are a class of covalently closed single-stranded that expressed during the development specific cells and tissues. CircRNAs play crucial roles in physiological pathological processes by sponging microRNAs, modulating gene transcription, controlling activity certain RNA-binding proteins, producing functional peptides. A key focus research at present is functionality circRNAs nervous system several advances have emerged over last 2 years. However, precise role has yet to be comprehensively reviewed. In this review, we first summarize recently described brain development, maturity, aging. Then, on involvement various diseases central system, such as cancer, chronic neurodegenerative diseases, acute injuries neuropathic pain. better understanding will help us develop potential diagnostic, prognostic, therapeutic strategies treat system.

Язык: Английский

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Insights into the Roles of Epigenetic Modifications in Ferroptosis

Biology, Год журнала: 2024, Номер 13(2), С. 122 - 122

Опубликована: Фев. 15, 2024

Ferroptosis is a non-apoptotic mode of cell death driven by membrane lipid peroxidation and characterized elevated intracellular levels Fe

Язык: Английский

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The landscape of circRNAs in gliomas temozolomide resistance: Insights into molecular pathways

Non-coding RNA Research, Год журнала: 2024, Номер 9(4), С. 1178 - 1189

Опубликована: Май 21, 2024

As the deadliest type of primary brain tumor, gliomas represent a significant worldwide health concern. Circular RNA (circRNA), unique non-coding molecule, seems to be one most alluring target molecules involved in pathophysiology many kinds cancers. CircRNAs have been identified as prospective targets and biomarkers for diagnosis treatment numerous disorders, particularly malignancies. Recent research has established clinical link between temozolomide (TMZ) resistance certain circRNA dysregulations glioma tumors. may play therapeutic role controlling or overcoming TMZ provide guidance novel kind individualized therapy. To address biological characteristics circRNAs their potential induce TMZ, this review highlighted summarized possible roles that molecular pathways drug resistance, including Ras/Raf/ERK PI3K/Akt signaling pathway metabolic processes gliomas.

Язык: Английский

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