Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Ноя. 29, 2024

Cell death is a fundamental part of life for metazoans. To maintain the balance between cell proliferation and metabolism human bodies, certain number cells need to be removed regularly. Hence, mechanisms have been preserved during evolution multicellular organisms. Tumorigenesis closely related with exceptional inhibition death. Mutations or defects in death-related genes block elimination abnormal enhance resistance malignant chemotherapy. Therefore, investigation enables development drugs that directly induce tumor In guidelines updated by Death Nomenclature Committee (NCCD) 2018, was classified into 12 types according morphological, biochemical functional classification, including intrinsic apoptosis, extrinsic mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, PARP-1 parthanatos, entotic death, NETotic lysosome-dependent autophagy-dependent immunogenic cellular senescence mitotic catastrophe. The mechanistic relationships epigenetic controls cancer progression were previously unclear. this review, we will summarize pathways corresponding regulations. Also, explore extensive interactions these discuss epigenetics which bring benefits therapy.

Язык: Английский

---

A deep insight into ferroptosis in lung disease: facts and perspectives

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Март 18, 2024

In the last decade, ferroptosis has received much attention from scientific research community. It differs other modes of cell death at morphological, biochemical, and genetic levels. Ferroptosis is mainly characterized by non-apoptotic iron-dependent caused lipid peroxide excess accompanied abnormal iron metabolism oxidative stress. recent years, more studies have shown that closely related to occurrence development lung diseases. COPD, asthma, injury, fibrosis, cancer, infection respiratory diseases become third most common chronic worldwide, bringing serious economic psychological burden people around world. However, exact mechanism which involved in progression not been fully revealed. this manuscript, we describe ferroptosis, targeting signaling pathways proteins, summarize relationship between diseases, explore intervention targeted therapy for

Язык: Английский

---

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

---

DNMT aberration-incurred GPX4 suppression prompts osteoblast ferroptosis and osteoporosis

Bone Research, Год журнала: 2024, Номер 12(1)

Опубликована: Дек. 1, 2024

Abstract Osteoporosis (OP) is a common and fracture-prone skeletal disease characterized by deteriorated trabecular microstructure pathologically involving various forms of regulated bone cell death. However, the exact role, cellular nature regulatory mechanisms ferroptosis in OP are not fully understood. Here, we reported that femurs from ovariectomized (Ovx) mice exhibited pronounced iron deposition, ferroptosis, transcriptional suppression key anti-ferroptotic factor GPX4 (glutathione peroxidase 4). was accompanied hypermethylation Gpx4 promoter an increase DNA methyltransferases DNMT1/3a/3b transcriptionally promoted repressive KLF5 corepressors NCoR SnoN. Conversely, DNMT inhibition with SGI-1027 reversed hypermethylation, ferroptotic osteoporosis. In cultured primary cells, ferric ammonium citrate (FAC) mimicking loading similarly induced osteoblasts but osteoclasts, which were rescued siRNA-mediated individual knockdown 1/3a/3b. Intriguingly, alleviated changes caused FAC, inactivator RSL3. More importantly, generated strain osteoblast-specific haplo-deficient Ob+/− developed spontaneous more severe alterations after Ovx operation, showed inactivation RSL3 or semi-knockout largely abolished osteoprotective effects SGI-1027. Taken together, our data suggest epigenetic aberration resulting osteoblastic contribute significantly to pathogenesis, strategies preserving intervention potentially effective treat related disorders.

Язык: Английский

---

Therapeutic effect of Ginkgetin on smoke-induced airway inflammation by down-regulating the c/EBPβ signaling pathway and CCL2 expression

Journal of Ethnopharmacology, Год журнала: 2024, Номер 331, С. 118284 - 118284

Опубликована: Май 10, 2024

Язык: Английский

---

Lipid peroxidation triggered by the degradation of xCT contributes to gasdermin D-mediated pyroptosis in COPD

Redox Biology, Год журнала: 2024, Номер 77, С. 103388 - 103388

Опубликована: Окт. 3, 2024

Язык: Английский

---

DNA dioxygenase TET2 deficiency aggravates sepsis-induced acute lung injury by targeting ITGA10 via the PI3K/AKT signaling pathway

Cellular & Molecular Biology Letters, Год журнала: 2025, Номер 30(1)

Опубликована: Май 19, 2025

Sepsis-induced acute lung injury (ALI) is a clinical condition with high morbidity and mortality, impaired endothelial function the main pathological characteristic. As member of DNA demethylases, ten-eleven translocation protein 2 (TET2) involved in variety biological processes. However, role TET2 dysfunction sepsis-induced ALI remains unclear. We used cecal ligation puncture (CLP) to establish mouse model screened out Tet2 from TET family proteins. The results suggested that was obviously declined. lipopolysaccharide (LPS) stimulate human pulmonary microvascular cells (HPMECs) as an vitro model, we found expression also decreased. Then small interfering RNAs adenovirus knockdown or overexpress investigate effect on HPMECs. changes symptoms were analyzed Tet2-deficient mice generated by adeno-associated virus 6 (AAV6). Next, RNA sequencing KEGG analysis find TET2-regulated downstream target genes signaling pathways under LPS stimulation. Finally, rescue experiments performed analyze modulated LPS-treated 5-hmC levels significantly decreased both vivo models ALI. exacerbated apoptosis HPMECs induced LPS. Conversely, overexpression alleviated these dysfunctions reduced apoptosis. Meanwhile, aggravated increased inflammation subsequent showed could increase Integrin α10 (ITGA10) reducing methylation level ITGA10 promoter. This, turn, activated PI3K-AKT pathway. Knocking down weakened beneficial effects LPS-stimulated cells. In our study, demonstrated deficiency aggravates cell promotes targeting via These findings indicate may be promising therapeutic for treating

Язык: Английский

---

The role of TET2 in solid tumors and its therapeutic potential: a comprehensive review

Clinical & Translational Oncology, Год журнала: 2024, Номер 26(9), С. 2156 - 2165

Опубликована: Апрель 10, 2024

Язык: Английский

---

Low TET1 Expression Levels in COPD Are Associated with Airway and Blood Neutrophilia

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 16, 2025

Abstract Epigenetic dysregulation, particularly DNA methylation variations, is implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Ten-eleven translocation (TET) proteins (TET1, TET2, and TET3) regulate gene transcription. Impaired TET1 expression was previously associated with airway inflammation asthma. Here we investigated TET associations COPD severity. We found that reduced peripheral blood mononuclear cells higher sputum neutrophil counts, decreased lung function increased severity patients. These findings support a potential protective role warrant further mechanistic investigations into actions COPD.

Язык: Английский

---

Sestrin2 alleviates cognitive impairment via inhibiting hippocampus ferroptosis in cigarette smoke-induced chronic obstructive pulmonary disease

Redox Biology, Год журнала: 2025, Номер unknown, С. 103673 - 103673

Опубликована: Май 1, 2025

Язык: Английский

---