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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Cancer-associated fibroblasts impair the cytotoxic function of NK cells in gastric cancer by inducing ferroptosis via iron regulation

Redox Biology, Journal Year: 2023, Volume and Issue: 67, P. 102923 - 102923

Published: Oct. 6, 2023

As the predominant immunosuppressive component within tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) inhibit Natural Killer cell (NK cell) activity to promote progression and immune escape; however, mechanisms of cross-talk between CAFs NK cells in gastric cancer (GC) remain poorly understood. In this study, we demonstrate that levels are inversely correlated with abundance human GC. impair anti-tumor capacity by inducing ferroptosis, a death process characterized accumulation iron-dependent lipid peroxides. induce ferroptosis promoting iron overload; conversely, decreased intracellular protect against CAF-induced ferroptosis. Mechanistically, increase labile pool via export into TME, which is mediated upregulated expression regulatory genes ferroportin1 hephaestin CAFs. Moreover, CAF-derived follistatin like protein 1(FSTL1) upregulates NCOA4 DIP2A-P38 pathway, NCOA4-mediated ferritinophagy required for patient-derived organoid model, functional targeting using combination deferoxamine FSTL1-neutralizing antibody significantly alleviate boost cytotoxicity This study demonstrates novel mechanism suppression TME presents potential therapeutic approach augment response GC cells.

Language: Английский

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Exosomal miR-223-3p from bone marrow mesenchymal stem cells targets HDAC2 to downregulate STAT3 phosphorylation to alleviate HBx-induced ferroptosis in podocytes

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

Published: Feb. 20, 2024

Background: Hepatitis B virus associated-glomerulonephritis (HBV-GN) is one of the major secondary renal diseases in China, and microRNAs (miRNAs) bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exo) can attenuate HBV-X protein (HBx)-induced ferroptosis podocytes, but exact mechanism remains unclear. This study aimed to investigate protective miR-223-3p BMSC-Exo HBx-induced podocytes. Methods: The employed human podocyte cells (HPCs), marrow-derived (BMSCs), as well kidney tissue from C57BL/6 mice HBx transgenic mice. Initially, correlation between STAT3 phosphorylation was authenticated through administration signal transducer activator transcription 3 (STAT3) inhibitors both vivo vitro settings. Furthermore, effect HDAC2 overexpression on examined. Subsequently, association carrying miR-223-3p, HDAC2, HPCs injury induced by assessed. interaction confirmed via RNA immunoprecipitation assay. Various techniques such cell counting kit-8 assay, western blot, RT-qPCR, immunofluorescence, flow cytometry, lipid peroxidation assay kit, iron transmission electron microscopy, hematoxylin-eosin staining were visualize extent . Results: attenuation be achieved inhibiting podocytes HBx. Conversely, upregulation enhance phosphorylation, thereby promoting ferroptosis. MiR-223-3p capable directly exerting negative regulation expression. effectively suppress expression ultimately leading reduce targeting with downregulating phosphorylation. Conclusion: evidences potential mediated delivery mitigating offering a novel therapeutic target approach for treating HBV-GN alleviating injury.

Language: Английский

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Ferroptosis in ulcerative colitis: Potential mechanisms and promising therapeutic targets

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116722 - 116722

Published: May 9, 2024

Ulcerative colitis (UC) is a complex immune-mediated chronic inflammatory bowel disease. It mainly characterized by diffuse inflammation of the colonic and rectal mucosa with barrier function impairment. Identifying new biomarkers for development more effective UC therapies remains pressing task current research. Ferroptosis newly identified form regulated cell death iron-dependent lipid peroxidation. As research deepens, ferroptosis has been demonstrated to be involved in pathological processes numerous diseases. A growing body evidence suggests that pathogenesis associated ferroptosis, regulation provides opportunities treatment. However, specific mechanisms which participates remain fully thoroughly investigated. Therefore, this review, we focus on advances mechanism recent years describe potential role UC. In addition, explore underlying crosslinked pathway between other such as macrophages, neutrophils, autophagy, endoplasmic reticulum stress, gut microbiota Finally, also summarize compounds may act inhibitors future.

Language: Английский

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Ferritinophagy: research advance and clinical significance in cancers

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

Published: Dec. 18, 2023

Ferritinophagy, a process involving selective autophagy of ferritin facilitated by nuclear receptor coactivator 4 (NCOA4), entails the recognition NCOA4 and subsequent delivery to autophagosome. Within autophagosome, undergoes degradation, leading release iron in lysosome. It is worth noting that excessive levels can trigger cell death. Recent evidence has elucidated significant roles played ferritinophagy ferroptosis regulation initiation progression cancer. Given crucial role tumor biology, it may serve as potential target for future anti-tumor therapeutic interventions. In this study, we have provided distinctive features its distinctions from ferroptosis. Moreover, briefly examined fundamental regulatory mechanisms ferritinophagy, encompassing involvement specific NCOA4, Nrf2/HO-1 signaling other pathways. Subsequently, synthesized current understanding impact on cancer applications, with particular emphasis utilization chemotherapy, nanomaterials, immunotherapy pathway purposes.

Language: Английский

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Cardiomyocyte LGR6 alleviates ferroptosis in diabetic cardiomyopathy via regulating mitochondrial biogenesis

Metabolism, Journal Year: 2024, Volume and Issue: 159, P. 155979 - 155979

Published: July 20, 2024

Language: Английский

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Inhibition of ER stress using tauroursodeoxycholic acid rescues obesity-evoked cardiac remodeling and contractile anomalies through regulation of ferroptosis

Chemico-Biological Interactions, Journal Year: 2024, Volume and Issue: 398, P. 111104 - 111104

Published: June 19, 2024

Language: Английский

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Ferroptosis and pyroptosis are connected through autophagy: a new perspective of overcoming drug resistance

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 17, 2025

Drug resistance is a common challenge in clinical tumor treatment. A reduction drug sensitivity of cells often accompanied by an increase autophagy levels, leading to autophagy-related resistance. The effectiveness combining chemotherapy drugs with inducers/inhibitors has been widely confirmed, but the mechanisms are still unclear. Ferroptosis and pyroptosis can be affected various types autophagy. Therefore, ferroptosis have crosstalk via autophagy, potentially switch cell death under certain conditions. As two forms inflammatory programmed death, different effects on inflammation, cGAS-STING signaling pathway also involved. it plays important role progression some chronic diseases. This review discusses relationship between pyroptosis, attempts uncover reasons behind evasion nature

Language: Английский

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SS-31@Fer-1 Alleviates ferroptosis in hypoxia/reoxygenation cardiomyocytes via mitochondrial targeting

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 183, P. 117832 - 117832

Published: Jan. 22, 2025

Language: Английский

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Autophagy in High-Fat Diet and Streptozotocin-Induced Metabolic Cardiomyopathy: Mechanisms and Therapeutic Implications

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1668 - 1668

Published: Feb. 15, 2025

Metabolic cardiomyopathy, encompassing diabetic and obese is an escalating global health concern, driven by the rising prevalence of metabolic disorders such as insulin resistance, type 1 2 diabetes, obesity. These conditions induce structural functional alterations in heart, including left ventricular dysfunction, fibrosis, ultimately heart failure, particularly presence coronary artery disease or hypertension. Autophagy, a critical cellular process for maintaining cardiac homeostasis, frequently disrupted cardiomyopathy. This review explores role autophagy pathogenesis high-fat diet (HFD) streptozotocin (STZ)-induced focusing on non-selective selective pathways, mitophagy, ER-phagy, ferritinophagy. Key proteins genes PINK1, Parkin, ULK1, AMPK, mTOR, ATG7, ATG5, Beclin-1, miR-34a are central to regulation Dysregulated autophagic flux impairs mitochondrial function, promotes oxidative stress, drives fibrosis heart. Additionally, processes lipophagy, regulated PNPLA8, ferritinophagy, modulated NCOA4, play pivotal roles lipid metabolism iron homeostasis. Emerging therapeutic strategies targeting autophagy, plant extracts (e.g., curcumin, dihydromyricetin), endogenous compounds sirtuin 3, LC3), lipid/glucose-lowering drugs, offer promising avenues mitigating effects Despite recent advances, precise mechanisms underlying this context remain poorly understood. A deeper understanding autophagy's regulatory networks, involving these proteins, may lead novel approaches treating

Language: Английский

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