Acyl-CoA synthase ACSL4: an essential target in ferroptosis and fatty acid metabolism

Chinese Medical Journal, Год журнала: 2023, Номер unknown

Опубликована: Июль 6, 2023

Long-chain acyl-coenzyme A (CoA) synthase 4 (ACSL4) is an enzyme that esterifies CoA into specific polyunsaturated fatty acids, such as arachidonic acid and adrenic acid. Based on accumulated evidence, the ACSL4-catalyzed biosynthesis of arachidonoyl-CoA contributes to execution ferroptosis by triggering phospholipid peroxidation. Ferroptosis a type programmed cell death caused iron-dependent peroxidation lipids; ACSL4 glutathione peroxidase positively negatively regulate ferroptosis, respectively. In addition, essential regulator (FA) metabolism. remodels composition membranes, regulates steroidogenesis, balances eicosanoid biosynthesis. ACSL4-mediated metabolic reprogramming antitumor immunity have attracted much attention in cancer biology. Because it facilitates cross-talk between FA metabolism, also research hotspot diseases ischemia/reperfusion injuries. this review, we focus structure, biological function, unique role ASCL4 various human diseases. Finally, propose might be potential therapeutic target.

Язык: Английский

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Ferroptosis, Necroptosis, and Pyroptosis in Gastrointestinal Cancers: The Chief Culprits of Tumor Progression and Drug Resistance

Advanced Science, Год журнала: 2023, Номер 10(26)

Опубликована: Июль 12, 2023

In recent years, the incidence of gastrointestinal cancers is increasing, particularly in younger population. Effective treatment crucial for improving patients' survival outcomes. Programmed cell death, regulated by various genes, plays a fundamental role growth and development organisms. It also critical maintaining tissue organ homeostasis takes part multiple pathological processes. addition to apoptosis, there are other types programmed such as ferroptosis, necroptosis, pyroptosis, which can induce severe inflammatory responses. Notably, besides pyroptosis contribute occurrence cancers. This review aims provide comprehensive summary on biological roles molecular mechanisms well their regulators hope open up new paths tumor targeted therapy near future.

Язык: Английский

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The crosstalk between exosomal miRNA and ferroptosis: A narrative review

Biology of the Cell, Год журнала: 2025, Номер 117(1)

Опубликована: Янв. 1, 2025

Ferroptosis is a type of cell death that multiple mechanisms and pathways contribute to the positive negative regulation it. For example, increased levels reactive oxygen species (ROS) induce ferroptosis. ferroptosis unlike apoptosis, it not dependent on caspases, but iron. Exosomes are membrane-bound vesicles with size about 30 150 nm, contain various cellular components, including DNA, RNA, microRNAs (miRNAs), lipids, proteins, which genetically similar their cells origin. found in all bodily fluids, blood, saliva, urine. Cells often release exosomes after fusion membrane. They play an important role immune cell-cell communication. miRNAs, noncoding RNAs length 18 24 nucleotides, involved regulating gene expression transcription. Emerging data suggests exosomal miRNAs implicated pathophysiological cells, metastasis, drug resistance, death. In addition, functional studies have indicated can key modulation by Therefore, this review, given importance ferroptosis, we decided elucidate relationship between diseases.

Язык: Английский

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Exosomal miR-142-3p secreted by hepatitis B virus (HBV)-hepatocellular carcinoma (HCC) cells promotes ferroptosis of M1-type macrophages through SLC3A2 and the mechanism of HCC progression

Journal of Gastrointestinal Oncology, Год журнала: 2022, Номер 13(2), С. 754 - 767

Опубликована: Апрель 1, 2022

Background: Most patients with hepatitis B virus (HBV) infection will develop hepatocellular carcinoma (HCC). This study aimed to explore the potential mechanism of miR-142-3p in HCC caused by HBV infection. Methods: HepG2 cells and M1 macrophages were cocultured then infected establish an vitro model. MicroRNA (miRNA) messenger RNA (mRNA) expression was analyzed quantitative reverse transcription polymerase chain reaction (RT-qPCR) Western blot. The protein expressions COX2, ACSL4, PTGS2, GPX4, NOX1 Flow cytometry TUNEL assays used assess cell reactive oxygen species (ROS) ferroptosis, respectively. Cell invasion migration measured Transwell assay. To evaluate ferroptosis M1-type macrophages, glutathione (GSH), malondialdehyde (MDA), Fe2+ content detected corresponding kits. Dual luciferase reporter gene detection verified targeting relationship between SLC3A2. Results: MiR-142-3p highly expressed HBV-infected macrophages. Inhibition or overexpression SLC3A2 reversed inhibited proliferation, migration, cells. Conclusions: Our findings indicated that promoted macrophage through SLC3A2, affecting production GSH, MDA, accelerating development HCC. regulation its target genes help clarify pathogenesis induced provide new theoretical foundations therapeutic targets.

Язык: Английский

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Ferroptosis: Biology and Role in Gastrointestinal Disease

Gastroenterology, Год журнала: 2024, Номер 167(2), С. 231 - 249

Опубликована: Март 1, 2024

Язык: Английский

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Targeting the regulation of iron homeostasis as a potential therapeutic strategy for nonalcoholic fatty liver disease

Metabolism, Год журнала: 2024, Номер 157, С. 155953 - 155953

Опубликована: Июнь 15, 2024

Язык: Английский

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Biological impact and therapeutic implication of tumor-associated macrophages in hepatocellular carcinoma

Cell Death and Disease, Год журнала: 2024, Номер 15(7)

Опубликована: Июль 12, 2024

The tumor microenvironment is a complex space comprised of normal, cancer and immune cells. macrophages are considered as the most abundant cells in their function tumorigenesis interesting. Macrophages can be present M1 M2 polarization that show anti-cancer oncogenic activities, respectively. Tumor-associated (TAMs) mainly have they increase due to secretion factors, cytokines affecting molecular pathways. Hepatocellular carcinoma (HCC) among predominant tumors liver spite understanding its pathogenesis, role progression still requires more attention. presence TAMs HCC causes an growth invasion one reasons induction glycolysis such metabolic reprogramming makes distinct from normal promotes malignancy. Since stimulates HCC, networks regulating conversion been highlighted moreover, drugs compounds with ability targeting suppressing phenotypes or at least activity utilized. aggressive behavior biological functions result development therapy resistance. provide cell-cell communication by secreting exosomes having various types biomolecules transfer change activity. Finally, non-coding RNA transcripts affect HCC.

Язык: Английский

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Intercellular crosstalk between cancer cells and cancer-associated fibroblasts via exosomes in gastrointestinal tumors

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Фев. 23, 2024

Gastrointestinal (GI) tumors are a significant global health threat, with high rates of morbidity and mortality. Exosomes contain various biologically active molecules like nucleic acids, proteins, lipids can serve as messengers for intercellular communication. They play critical roles in the exchange information between tumor cells microenvironment (TME). The TME consists mesenchymal components extracellular matrix (ECM), fibroblasts being most abundant cell type mesenchyme. Cancer-associated (CAFs) derived from normal stem that activated TME. CAFs secrete exosomes to modulate proliferation, invasion, migration, drug resistance, other biological processes tumors. Additionally, manipulate function behavior through direct cell-cell interactions. This review provides summary crosstalk GI exosomes, along potential underlying mechanisms.

Язык: Английский

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Targeting ferroptosis: the role of non-coding RNAs in hepatocellular carcinoma progression and therapy

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 16, 2025

Язык: Английский

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Aucubin Promotes BMSCs Proliferation and Differentiation of Postmenopausal Osteoporosis Patients by Regulating Ferroptosis and BMP2 Signalling

Journal of Cellular and Molecular Medicine, Год журнала: 2025, Номер 29(2)

Опубликована: Янв. 1, 2025

Postmenopausal osteoporosis (PMOP) is a chronic systemic bone metabolism disorder. Promotion in the patterns of human marrow mesenchymal stem cells (hBMSCs) differentiation towards osteoblasts contributes to alleviating osteoporosis. Aucubin, natural compound isolated from well-known herbal medicine Eucommia, was previously shown possess various pharmacological effects. However, its effects on hBMSCs PMOP patients are unknown. The aim this present research investigate impact and underlying process aucubin cell proliferation osteogenic patients. ability inhibit ferroptosis induced by erastin detected; ROS production, ferrous ion levels, SOD, MDA, GPX activities were tested using commercial kits. Next, ALP staining, ARS RT-qPCR, RNA-sequencing, Western blot applied for determining mRNA protein expression levels associated with osteogenesis hBMSCs. study also explored involvement BMP2/Smads signalling promoting evaluated intervention an ovariectomised rat model. results indicated that significantly inhibited generation oxidative stress protected against Additionally, facilitated activating BMP2/SMADs pathway attenuated progression OVX rats, suggesting potential therapeutic benefit postmenopausal (PMOP).

Язык: Английский

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