NEDD4L contributes to ferroptosis and cell growth inhibition in esophageal squamous cell carcinoma by facilitating xCT ubiquitination DOI Creative Commons
Zhen Chen, Weilong Wang,

Jinghan Hou

и другие.

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Ноя. 18, 2024

Abstract The oncogene xCT plays an indispensable role in tumor growth by protecting cancer cells from oxidative stress and ferroptosis. Emerging evidence indicated function is tightly controlled posttranslational modifications, especially ubiquitination. However, it still remains unclear what specific regulatory mechanism of ubiquitin ligases human cancers. Here, we reported that NEDD4L, E3 ligases, inhibited esophageal squamous cell carcinoma (ESCC) facilitated ferroptosis ubiquitination xCT. NEDD4L expression was declined ESCC associated with invasion, lymph node metastasis distant metastasis. Silencing triggered growth. Meanwhile, knock down prevented the accumulation ROS, elevated level GSH, reduced content MDA cells, thereby inhibiting Mechanistically, directly bound to ∆CT domain through its WW HECT domain. More importantly, promoted degradation facilitating polyubiquitination cells. Collectively, these findings suggest crucial governing stability mediating ESCC.

Язык: Английский

Dexmedetomidine plays a protective role in sepsis-associated myocardial injury by repressing PRMT5-mediated ferroptosis. DOI
Dan Wang, Jun Wang, Li Yang

и другие.

PubMed, Год журнала: 2025, Номер 14(1), С. tfaf010 - tfaf010

Опубликована: Фев. 1, 2025

Sepsis rapidly contributed to multiorgan failure, most typically damaging the cardiovascular system, and there were no effective treatments. Dexmedetomidine (Dex) has good therapeutic effects on sepsis-induced organ injury. Our work aimed probe pharmacological of Dex ferroptosis in sepsis-associated myocardial injury (S-MI) define underlying mechanism action. Cardiomyocytes exposed lipopolysaccharide (LPS) for mimicking S-MI model vitro. The septic mice constructed by cecum ligation puncture operation. mRNA protein expressions assessed using quantitative real-time polymerase chain reaction or western blot. Cell survival was determined cell counting kit-8, lactic dehydrogenase release, flow cytometry assays. 2',7'-Dichlorodihydrofluorescein diacetate staining measured cellular reactive oxygen species level. secretion levels inflammatory cytokines, ferroptosis-related indicators analyzed enzyme-linked immunosorbent assay. N6-methyladenosine (m6A) modification level arginine methyltransferase 5 (PRMT5) examined methylated RNA binding immunoprecipitation (Me-RIP) interaction between like 3 (METTL3)/fat mass obesity-associated (FTO) PRMT5 treatment alleviated LPS-induced cardiomyocyte ferroptosis, while these reversed Erastin treatment. Mechanically, ameliorated expression cardiomyocytes regulating METTL3/FTO catalyzed m6A mRNA. Rescue experiments confirmed that overexpression abolished Dex-mediated inhibitory roles ferroptosis. Moreover, administration inflammation, mice. Taken together, repressed PMRT5 a m6A-dependent manner, thus lightening LPS-triggered alleviate

Язык: Английский

Процитировано

0
Radioactive Diselenide Bonded Covalent Organic Framework DOI Open Access
Liang Zhang, Shuo Wang,

Qi‐Chao Yang

и другие.

Advanced Materials, Год журнала: 2025, Номер unknown

Опубликована: Фев. 23, 2025

Covalent organic frameworks (COFs) are porous crystals of high potential in biomedical applications. The chemical bonds within COF structures critical for the overall therapeutic performance. Here, design and synthesis radioactive reported by introducing labile diselenide into structure backbone. This bonded COF, PorSe-CuPt, constructed from Cu Pt ion porphyrin units, is capable bond cleavage upon irradiation, thus releasing drug molecule, CBL0137, carried pores. Concerted with promotion X-ray absorption Pt2⁺ enrichment oxygen Cu2⁺, robust PANoptosis achieved as well improved immunosuppressive tumor microenvironment, thereby drastically enhancing effectiveness radiotherapy. integration backbone demonstrates possible application clip-off chemistry search highly responsible compatible biomaterials.

Язык: Английский

Процитировано

0
CHI3L1 mediates radiation resistance in colorectal cancer by inhibiting ferroptosis via the p53/SLC7A11 pathway DOI Creative Commons
Ming Jin, Hui Liu, Zhen Zheng

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Март 21, 2025

Radiotherapy is a key treatment for colorectal cancer (CRC), particularly rectal cancer; however, many patients are resistant to radiation. While it has been shown that CHI3L1 associated with CRC progression, its specific function and regulatory mechanisms in radiation resistance remain unclear. The levels of normal tissue samples were obtained from Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) datasets. To assess the effects on cell proliferative, migratory, invasive capacities, Cell Counting Kit-8 (CCK-8) Transwell assays performed. Radiation cells varying expression was evaluated through colony formation assay. Western blot immunofluorescence analyses conducted explore correlation between p53 levels. Ferroptosis assessed by determining reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) concentrations different levels, xenograft mouse model used identify molecular ferroptosis vivo. Significant upregulated observed tissues promotion malignant behaviors. number colonies CHI3L1-overexpressing groups significantly greater than control following radiation, indicating increased former group. Furthermore, overexpression downregulation elevated ubiquitination. Notably, inhibited suppressing p53/SLC7A11 signaling pathway. promotes proliferation, migration, invasion, cells. Elevated ubiquitination SLC7A11 upregulation. axis.

Язык: Английский

Процитировано

0
Identification and exploration of key genes associated with radioresistance in lung adenocarcinoma DOI Creative Commons
Ying Wang, Yangyang Shang,

Mingyu Hua

и другие.

Cancer Cell International, Год журнала: 2025, Номер 25(1)

Опубликована: Апрель 19, 2025

Radiation resistance in lung adenocarcinoma (LUAD) remains a primary obstacle limiting radiotherapy efficacy. However, the detailed factors and molecular mechanisms influencing LUAD radiosensitivity are not fully understood. Radioresistance-related genes (RRRGs) were screened by RNA sequencing bioinformatics analysis, prediction model for efficacy was developed via LASSO-Cox regression analysis. We specifically focused on Stanniocalcin 2 (STC2) due to its prognostic significance validated expression through immunohistochemical staining (IHC) pathological samples from patients. A STC2 knockdown (siSTC2) A549 cell line created, Western blotting, CCK8, colony formation assays performed investigate STC2's involvement radioresistance. An constructed using 6 RRRGs (FCGBP, SLCO4A1, ALDH3A1, STC2, TERT, CYP24A1). IHC analysis of 74 patients showed significantly higher non-responders (N-Res) versus responders (Res) (p < 0.05). Patients with elevated levels experienced shorter overall survival (OS). blotting revealed irradiated (IR) cells compared non-irradiated (N-IR) CCK8 results suggested that resulted significant reduction proliferation ability 0.05), confirmed decrease clonogenic siSTC2 controls plays role mediating radioresistance, high correlating poor prognosis. Therefore, represents promising therapeutic target overcoming Not applicable.

Язык: Английский

Процитировано

0
The AEG-1-USP10-PARP1 axis confers radioresistance in esophageal squamous cell carcinoma via facilitating homologous recombination-dependent DNA damage repair DOI Creative Commons
Xu Zhao, Yuan Ma, Jing Li

и другие.

Cancer Letters, Год журнала: 2023, Номер 577, С. 216440 - 216440

Опубликована: Окт. 12, 2023

Radiotherapy is the standard adjuvant treatment for esophageal squamous cell carcinoma (ESCC), yet radioresistance remains a major obstacle leading to failure and unfavorable prognosis. Previous reports have demonstrated involvement of astrocyte elevated gene-1 (AEG-1) in tumorigenesis progression multiple malignancies. Nevertheless, precise role AEG-1 ESCC elusive. Here, we unveiled strong correlation between aberrant gene overexpression malignant as well adverse prognosis patients. Moreover, both vitro vivo investigations revealed that significantly alleviated irradiation-induced DNA damage enhanced radiation resistance cells. Mechanistically, recruited deubiquitinase USP10 remove K48-linked polyubiquitin chains at Lys425 PARP1, thus preventing its proteasomal degradation. This orchestrated process facilitated homologous recombination-mediated double-strand breaks (DSBs) repair, culminating mitigated acquired Notably, PARP1 reversed radiosensitizing effect caused by deficiency. Collectively, these findings shed new light on mechanism radioresistance, providing potential therapeutic targets enhance efficacy radiotherapy ESCC.

Язык: Английский

Процитировано

10
Ferroptosis: Potential opportunities for natural products in cancer therapy DOI

Anzheng Nie,

Chaozan Shen,

Zheng Zhou

и другие.

Phytotherapy Research, Год журнала: 2023, Номер 38(3), С. 1173 - 1190

Опубликована: Дек. 20, 2023

Abstract Cancer cells often exhibit defects in the execution of cell death, resulting poor clinical outcomes for patients with many cancer types. Ferroptosis is a newly discovered form programmed death characterized by intracellular iron overload and lipid peroxidation membrane. Increasing evidence suggests that ferroptosis closely associated wide variety physiological pathological processes, particularly cancer. Notably, various bioactive natural products have been shown to induce initiation cells, thereby exerting anticancer effects. In this review, we summarize core regulatory mechanisms multifaceted roles Importantly, focus on regulate such as terpenoids, polyphenols, alkaloids, steroids, quinones, polysaccharides. The efficacy, adverse effects, drug–drug interactions these need be evaluated further high‐quality studies accelerate their application treatment.

Язык: Английский

Процитировано

9
High expression of PPP1CC promotes NHEJ-mediated DNA repair leading to radioresistance and poor prognosis in nasopharyngeal carcinoma DOI
Ping Feng, Ying Wang, Na Liu

и другие.

Cell Death and Differentiation, Год журнала: 2024, Номер 31(5), С. 683 - 696

Опубликована: Апрель 8, 2024

Язык: Английский

Процитировано

3
Unveiling autophagy complexity in leukemia: The molecular landscape and possible interactions with apoptosis and ferroptosis DOI
Young Yun Jung, Kwang Seok Ahn, Mingzhi Shen

и другие.

Cancer Letters, Год журнала: 2023, Номер 582, С. 216518 - 216518

Опубликована: Дек. 2, 2023

Язык: Английский

Процитировано

8
Ferroptosis: Molecular perspective, cellular influence, cancer manifestation, and therapeutic potentials DOI
Pawan Kumar Pandey,

Saurabh Bhorkade,

Shikha Jha

и другие.

Journal of Drug Delivery Science and Technology, Год журнала: 2024, Номер 100, С. 105998 - 105998

Опубликована: Июль 31, 2024

Язык: Английский

Процитировано

2
CRISPR screening identifies PRMT1 as a key pro-ferroptotic gene via a two-layer regulatory mechanism DOI Creative Commons
Xin Zhang, Yajun Duan, Li Su

и другие.

Cell Reports, Год журнала: 2024, Номер 43(9), С. 114662 - 114662

Опубликована: Авг. 23, 2024

Ferroptosis is a form of nonapoptotic cell death characterized by iron-dependent peroxidation polyunsaturated phospholipids. However, much remains unknown about the regulators ferroptosis. Here, using CRISPR-Cas9-mediated genetic screening, we identify protein arginine methyltransferase 1 (PRMT1) as crucial promoter We find that PRMT1 decreases expression solute carrier family 7 member 11 (SLC7A11) to limit abundance intracellular glutathione (GSH). Moreover, show interacts with ferroptosis suppressor (FSP1), GSH-independent suppressor, inhibit membrane localization and enzymatic activity FSP1 through dimethylation at R316, thus reducing CoQ10H2 content inducing sensitivity. Importantly, depletion or pharmacological inhibition in mice prevents ferroptotic events liver improves overall survival under concanavalin A (ConA) exposure. Hence, our findings suggest key regulator potential target for antiferroptosis therapeutics.

Язык: Английский

Процитировано

2