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

---

The mechanism of ferroptosis and its related diseases

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Oct. 16, 2023

Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.

Language: Английский

---

The role of molecular subtypes and immune infiltration characteristics based on disulfidptosis-associated genes in lung adenocarcinoma

Aging, Journal Year: 2023, Volume and Issue: unknown

Published: June 13, 2023

Lung adenocarcinoma (LUAD) is the most common type of lung cancer which accounts for about 40% all cancers. Early detection, risk stratification and treatment are important improving outcomes LUAD. Recent studies have found that abnormal accumulation cystine other disulfide occurs in cell under glucose starvation, induces stress increases content bond actin cytoskeleton, resulting death, defined as disulfidptosis. Because study disulfidptosis its infancy, role disease progression still unclear. In this study, we detected expression mutation genes LUAD using a public database. Clustering analysis based on gene was performed differential subtype were analyzed. 7 used to construct prognostic model, causes differences investigated by immune-infiltration analysis, immune checkpoint drug sensitivity analysis. qPCR verify key line (A549) normal bronchial epithelial (BEAS-2B). Since G6PD had highest factor cancer, further verified protein cells western blot, confirmed through colony formation experiment interference with able significantly inhibit proliferation ability cells. Our results provide evidence new ideas individualized precision therapy

Language: Английский

---

Neutrophil extracellular traps promote growth of lung adenocarcinoma by mediating the stability of m6A‐mediated SLC2A3 mRNA‐induced ferroptosis resistance and CD8(+) T cell inhibition

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(2)

Published: Jan. 26, 2025

Abstract To investigate the potential mechanisms underlying neutrophil extracellular traps (NETs) confer ferroptosis resistance and CD8(+) T cell inhibition in lung adenocarcinoma (LUAD). By intravenous injection of LLC cells into tail vein, a LUAD mouse model was created. Phorbol‐12‐myristate‐13‐acetate (PMA) stimulated neutrophils to facilitate NETs formation combined with inhibitor DNase I explore mechanism on proliferation, migration, resistance, activity. CitH3, myeloperoxidase (MPO), cell‐free DNA, MPO‐DNA levels were increased, indicating an increase LUAD. PMA promoted tumours mice, increased number CD3(+)CD4(+) cells, decreased perforin, granzyme A, B, IFNγ, TNF‐α levels, growth tumour nodules, that formation, reduced activity CD8(+)T growth. partially reversed effects PMA. proliferation while effects. Erastin inhibited migration ferroptosis. Further results showed by promoting YTHDF2‐mediated SLC2A3 mRNA degradation. Sh‐YTHDF2 effect whereas si‐SLC2A3 sh‐YTHDF2 cells. In addition, inhibiting tumours, Our suggested through

Language: Английский

---

Regulation of Ferroptosis in Lung Adenocarcinoma

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14614 - 14614

Published: Sept. 27, 2023

Lung adenocarcinoma (LUAD) is the most common lung cancer, which accounts for about 35-40% of all cancer patients. Despite therapeutic advancements in recent years, overall survival time LUAD patients still remains poor, especially KRAS mutant LUAD. Therefore, it necessary to further explore novel targets and drugs improve prognos Ferroptosis, an iron-dependent regulated cell death (RCD) caused by lipid peroxidation, has attracted much attention recently as alternative target apoptosis therapy. Ferroptosis been found be closely related at every stage, including initiation, proliferation, progression. In this review, we will provide a comprehensive overview ferroptosis mechanisms, its regulation LUAD, application targeting

Language: Английский

---

Effects of DNA, RNA, and Protein Methylation on the Regulation of Ferroptosis

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(11), P. 3558 - 3575

Published: Jan. 1, 2023

Ferroptosis is a form of programmed cell death characterized by elevated intracellular ferrous ion levels and increased lipid peroxidation.Since its discovery characterization in 2012, considerable progress has been made understanding the regulatory mechanisms pathophysiological functions ferroptosis.Recent findings suggest that numerous organ injuries (e.g., ischemia/reperfusion injury) degenerative pathologies aortic dissection neurodegenerative disease) are driven ferroptosis.Conversely, insufficient ferroptosis linked to tumorigenesis.Furthermore, recent study revealed effect on hematopoietic stem cells under physiological conditions.The identified date include mainly iron metabolism, such as transport ferritinophagy, redox systems, glutathione peroxidase 4 (GPX4)-glutathione (GSH), ferroptosis-suppressor-protein 1 (FSP1)-CoQ10, FSP1-vitamin K (VK), dihydroorotate dehydrogenase (DHODH)-CoQ, GTP cyclohydrolase (GCH1)-tetrahydrobiopterin (BH4).Recently, an increasing number studies have demonstrated important role played epigenetic mechanisms, especially DNA, RNA, protein methylation, ferroptosis.In this review, we provide critical analysis molecular networks date, with focus methylation.Furthermore, discuss some debated unanswered questions should be foci future research field.

Language: Английский

---

Targeting IGF2BP3 in Cancer

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(11), P. 9423 - 9423

Published: May 29, 2023

RNA-binding proteins (RBPs) can regulate multiple pathways by binding to RNAs, playing a variety of functions, such as localization, stability, and immunity. In recent years, with the development technology, researchers have discovered that RBPs play key role in N6-methyladenosine (m6A) modification process. M6A methylation is most abundant form RNA eukaryotes, which defined on sixth N atom adenine RNA. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) one components m6A proteins, plays an important decoding marks performing various biological functions. IGF2BP3 abnormally expressed many human cancers, often associated poor prognosis. Here, we summarize physiological organisms describe its mechanism tumors. These data suggest may be valuable therapeutic target prognostic marker future.

Language: Английский

---

CircNFATC3 promotes the proliferation of gastric cancer through binding to IGF2BP3 and restricting its ubiquitination to enhance CCND1 mRNA stability

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: June 20, 2023

Abstract Background Insulin like growth factor II mRNA binding protein 3 (IGF2BP3) is an RNA with multiple roles in regulation of gene expression at the post-transcriptional level and implicated tumorigenesis progression numerous cancers including gastric cancer (GC). Circular RNAs (circRNAs) are a diverse endogenous noncoding population that have important regulatory cancer. However, circRNAs regulate IGF2BP3 GC largely unknown. Methods CircRNAs bound to were screened cells using immunoprecipitation sequencing (RIP-seq). The identification localization circular nuclear activated T (circNFATC3) identified Sanger sequencing, RNase R assays, qRT-PCR, nuclear-cytoplasmic fractionation RNA-FISH assays. CircNFATC3 human tissues adjacent normal measured by qRT-PCR ISH. biological role circNFATC3 was confirmed vivo vitro experiments. Furthermore, RIP, RNA-FISH/IF, IP rescue experiments performed uncover interactions between circNFATC3, cyclin D1 (CCND1). Results We GC-associated circRNA, interacted IGF2BP3. significantly overexpressed positively associated tumor volume. Functionally, proliferation decreased after knockdown vitro. Mechanistically, cytoplasm, which enhanced stability preventing ubiquitin E3 ligase TRIM25-mediated ubiquitination, thereby enhancing axis IGF2BP3-CCND1 promoting CCND1 stability. Conclusions Our findings demonstrate promotes stabilizing enhance Therefore, potential novel target for treatment GC.

Language: Английский

---

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

---

The role and mechanism of m6A methylation in diabetic nephropathy

Life Sciences, Journal Year: 2025, Volume and Issue: 363, P. 123355 - 123355

Published: Jan. 6, 2025

Language: Английский

---