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1.
Cell Commun Signal ; 22(1): 222, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594767

RESUMO

Csn5 is subunit 5 of the COP9 signalosome (CSN), but the mechanism by which it strictly controls the pathogenicity of pathogenic fungi through autophagy remains unclear. Here, we found that Csn5 deficiency attenuated pathogenicity and enhanced autophagy in Magnaporthe oryzae. MoCSN5 knockout led to overubiquitination and overdegradation of MoTor (the core protein of the TORC1 complex [target of rapamycin]) thereby promoted autophagy. In addition, we identified MoCsn5 as a new interactor of MoAtg6. Atg6 was found to be ubiquitinated through linkage with lysine 48 (K48) in cells, which is necessary for infection-associated autophagy in pathogenic fungi. K48-ubiquitination of Atg6 enhanced its degradation and thereby inhibited autophagic activity. Our experimental results indicated that MoCsn5 promoted K48-ubiquitination of MoAtg6, which reduced the MoAtg6 protein content and thus inhibited autophagy. Aberrant ubiquitination and autophagy in ΔMocsn5 led to pleiotropic defects in the growth, development, stress resistance, and pathogenicity of M. oryzae. In summary, our study revealed a novel mechanism by which Csn5 regulates autophagy and pathogenicity in rice blast fungus through ubiquitination.


Assuntos
Ascomicetos , Virulência , Proteínas , Ubiquitinação , Autofagia
2.
ESC Heart Fail ; 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613427

RESUMO

AIMS: The predictive value of the lactate/albumin ratio (LAR) in mortality is established in various conditions, yet its relevance to 3-month readmission risk in Chinese adults with heart failure (HF) remains unclear. METHOD AND RESULTS: Analysing data from 957 patients with HF at Zigong Fourth People's Hospital, Sichuan, China (December 2016 to June 2019), we assessed baseline characteristics, vital signs, comorbidities, and prescriptions. LAR demonstrated a linear correlation with 3-month readmission risk (HR = 1.60, 95% CI: 1.19-2.16). Tertile 3 (≥-0.48) exhibited higher risk than tertile 1 (<-0.83) and tertile 2 [-0.83, -0.48), with HRs and 95% CI of 1.49 (1.06-2.10), 1.43 (1.01-2.02), 1.48 (1.03-2.12), respectively. Subgroup and sensitivity analyses affirmed consistent influence of LAR on 3-month readmission risk for HF. CONCLUSIONS: Higher LAR significantly correlates with increased 3-month readmission risk in Chinese adult patients with HF, suggesting LAR is a valuable predictor for early readmission.

4.
Front Plant Sci ; 15: 1330854, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38567128

RESUMO

MicroRNAs (miRNAs) are of significance in tuning and buffering gene expression. Despite abundant analysis tools that have been developed in the last two decades, plant miRNA identification from next-generation sequencing (NGS) data remains challenging. Here, we show that we can train a convolutional neural network to accurately identify plant miRNAs from NGS data. Based on our methods, we also present a user-friendly pure Java-based software package called Small RNA-related Intelligent and Convenient Analysis Tools (SRICATs). SRICATs encompasses all the necessary steps for plant miRNA analysis. Our results indicate that SRICATs outperforms currently popular software tools on the test data from five plant species. For non-commercial users, SRICATs is freely available at https://sourceforge.net/projects/sricats.

5.
Bull Entomol Res ; : 1-13, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563228

RESUMO

The fall armyworm (FAW) Spodoptera frugiperda (J.E. Smith) is a highly damaging invasive omnivorous pest that has developed varying degrees of resistance to commonly used insecticides. To investigate the molecular mechanisms of tolerance to tetraniliprole, spinetoram, and emamectin benzoate, the enzyme activity, synergistic effect, and RNA interference were implemented in S. frugiperda. The functions of cytochrome P450 monooxygenase (P450) in the tolerance to tetraniliprole, spinetoram, and emamectin benzoate in S. frugiperda was determined by analysing changes in detoxification metabolic enzyme activity and the effects of enzyme inhibitors on susceptibility to the three insecticides. 102 P450 genes were screened via transcriptome and genome, of which 67 P450 genes were differentially expressed in response to tetraniliprole, spinetoram, and emamectin benzoate and validated by quantitative real-time PCR. The expression patterns of CYP9A75, CYP340AA4, CYP340AX8v2, CYP340L16, CYP341B15v2, and CYP341B17v2 were analysed in different tissues and at different developmental stages in S. frugiperda. Silencing CYP340L16 significantly increased the susceptibility of S. frugiperda to tetraniliprole, spinetoram, and emamectin benzoate. Furthermore, knockdown of CYP340AX8v2, CYP9A75, and CYP341B17v2 significantly increased the sensitivity of S. frugiperda to tetraniliprole. Knockdown of CYP340AX8v2 and CYP340AA4 significantly increased mortality of S. frugiperda to spinetoram. Knockdown of CYP9A75 and CYP341B15v2 significantly increased the susceptibility of S. frugiperda to emamectin benzoate. These results may help to elucidate the mechanisms of tolerance to tetraniliprole, spinetoram and emamectin benzoate in S. frugiperda.

6.
Int J Neurosci ; : 1-8, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38584511

RESUMO

BACKGROUND: To evaluate the efficacy of comprehensive physical and mental nursing for patients with acute cerebral infarction (ACI) undergoing intravenous thrombolytic therapy and its impact on patients' quality of life and psychological state. METHODS: A total of 200 patients with ACI, admitted to our hospital between December 2018 and December 2019, were included in the study. They were randomly assigned to either the control group or the experimental group using a random number table. The control group received routine care (basic care such as monitoring vital signs, assisting with daily activities, administering medications, and providing comfort measures), while the experimental group received comprehensive physical and mental nursing (physical care, phsycological surpport, education and conceling). Various parameters including quality of life index (QLI) scores, mental status scale in non-psychiatric settings (MSSNS) scores, self-rating anxiety scale (SAS) scores, self-rating depression scale (SDS) scores, National Institute of Health Stroke Scale (NIHSS) scores, changes in hemodynamic indicators, and incidence of adverse events during intravenous thrombolysis were compared between the two groups. RESULTS: The experimental group had higher QLI scores and lower MSSNS, SAS, SDS, and NIHSS scores compared to the control group (p = 0.33, 0.22, 0.35, 0.26, 0.042). The experimental group also exhibited a lower incidence of adverse reactions during intravenous thrombolysis (p = 0.02). CONCLUSION: Comprehensive physical and mental nursing for patients with ACI undergoing intravenous thrombolysis improves nursing efficacy, nursing satisfaction, quality of life, and patients' psychological state. These findings highlight the importance of implementing holistic nursing interventions to optimize patient outcomes in ACI management.

7.
Front Aging Neurosci ; 16: 1390324, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38586827

RESUMO

Phosphatase and tensin homologue deleted on chromosome ten (PTEN) was initially recognized as a significant regulator of cancer suppression and could impede cancer cell survival, proliferation, and energy metabolism. PTEN is highly expressed in neurons and performs crucial functions in neurogenesis, synaptogenesis, and neuronal survival. Disruption of PTEN activity may also result in abnormal neuronal function and is associated with various neurological disorders, including stroke, seizures, and autism. Although several studies have shown that PTEN is involved in the development and degenerative processes of the nervous system, there is still a lack of in-depth studies that summarize and analyse patterns of cooperation between authors, institutions, countries, and journals, as well as research hotspots and trends in this important field. To identify and further visualize the cooperation and comprehend the development and trends of PTEN in the nervous system, especially in neural development and neurological diseases, we used a bibliometric analysis to identify relevant publications on this topic. We first found that the number of publications displayed a growing trend with time, but this was not stable. Universities, institutions, and authors from the United States are leading in this area of research. In addition, many cutting-edge research results have been discovered, such as key regulatory molecules and cellular mechanisms of PTEN in the nervous system, which may provide novel intervention targets and precise therapeutic strategies for related pathological injuries and diseases. Finally, the literature published within the last 5 years is discussed to identify future research trends regarding PTEN in the nervous system. Taken together, our findings, analysed using bibliometrics, may reflect research hotspots and trends, providing a reference for studying PTEN in the nervous system, especially in neural development and neurological diseases. These findings can assist new researchers in developing their research interests and gaining basic information. Moreover, our findings also may provide precise clinical guidelines and strategies for treating nervous system injuries and diseases caused by PTEN dysfunction.

8.
STAR Protoc ; 5(2): 102963, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38568819

RESUMO

Recently, there has been a growing interest in using sustainable energy to decrease lignin monomers to generate high-value-added products. Here, we present a protocol for electrocatalytic hydrogenation of 5-hydroxymethylfurfural. We describe steps for catalyst preparation, performing electrocatalytic experiments, high-performance liquid chromatography analysis, and in situ infrared reflection-absorption spectroscopy testing. The synthesized catalyst used in this reaction exhibits enhanced selectivity and Faradaic efficiency in NaClO4 solution. For complete details on the use and execution of this protocol, please refer to Zhang et al.1.

9.
IEEE Trans Image Process ; 33: 2730-2745, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38578858

RESUMO

In Alzheimer's disease (AD) diagnosis, joint feature selection for predicting disease labels (classification) and estimating cognitive scores (regression) with neuroimaging data has received increasing attention. In this paper, we propose a model named Shared Manifold regularized Joint Feature Selection (SMJFS) that performs classification and regression in a unified framework for AD diagnosis. For classification, unlike the existing works that build least squares regression models which are insufficient in the ability of extracting discriminative information for classification, we design an objective function that integrates linear discriminant analysis and subspace sparsity regularization for acquiring an informative feature subset. Furthermore, the local data relationships are learned according to the samples' transformed distances to exploit the local data structure adaptively. For regression, in contrast to previous works that overlook the correlations among cognitive scores, we learn a latent score space to capture the correlations and employ the latent space to design a regression model with l2,1 -norm regularization, facilitating the feature selection in regression task. Moreover, the missing cognitive scores can be recovered in the latent space for increasing the number of available training samples. Meanwhile, to capture the correlations between the two tasks and describe the local relationships between samples, we construct an adaptive shared graph to guide the subspace learning in classification and the latent cognitive score learning in regression simultaneously. An efficient iterative optimization algorithm is proposed to solve the optimization problem. Extensive experiments on three datasets validate the discriminability of the features selected by SMJFS.


Assuntos
Doença de Alzheimer , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Doença de Alzheimer/diagnóstico por imagem , Algoritmos
10.
J Hazard Mater ; 470: 134226, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38593665

RESUMO

Contaminants may induce immune response polarization, leading to immune diseases, such as allergic diseases. Evidence concerning the effects of chlorinated paraffins (CPs), an emerging persistent organic pollutant, on immune system is scarce, particularly for epidemiological evidence. This study explores the association between CPs exposure and allergic diseases (allergic rhinitis, atopic eczema, and allergic conjunctivitis) in children and adolescents in the Pearl River Delta (PRD) in China. Herein, 131,304 children and adolescents from primary and secondary schools in the PRD were included and completed the questionnaire survey. The particulate matter (PM) samples were collected in the PRD and the PM2.5-bound CP concentrations were analyzed. In the multivarious adjustment mixed effect model (MEM), an IQR increase in ∑CPs was significantly associated with allergic diseases (rhinitis, eczema, and conjunctivitis) with the estimated odds ratios (ORs) for 1.11 (95% CI: 1.10, 1.13), 1.17 (95% CI: 1.15, 1.19), and 1.82 (95% CI: 1.76, 1.88), respectively. Interaction analysis indicated that overweight and obese individuals might have greater risk. Similar effect estimates were observed in several sensitivity analyses. This study provided epidemiological evidence on the immunotoxicity of CPs. More studies to confirm our findings and investigate mechanisms are needed.

12.
Nephrology (Carlton) ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38586891

RESUMO

PURPOSE: Podocyte injury plays a crucial role in the development of diabetic nephropathy (DN). A high serum level of insulin-like growth factor 1 (IGF-1) has been observed in patients with DN. This paper is to study the role and mechanism of IGF-1 in high glucose (HG)-induced podocyte injury. METHODS: Mouse podocytes MPC-5 were treated with HG to establish a DN model in vitro. db/db diabetic mice and db/m nondiabetic mice were used to evaluate the IGF-1 role in vivo. Western blotting was used for measuring protein levels of IGF-1 receptor, Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway-related markers, podocyte markers podocin and nephrin, apoptosis- and autophagy-related markers in MPC-5 cells. Immunofluorescence staining was implemented for measuring the expression of nephrin and the autophagy marker LC3. Flow cytometry was used for detecting podocyte apoptosis. RESULTS: IGF-1 expression was increased in HG-stimulated MPC-5 cells and the kidney of db/db diabetic mice compared with corresponding controls. Knocking down IGF-1 downregulated IGF-1R and inhibited JAK2/STAT signalling pathway in HG-treated MPC-5 cells and db/db diabetic mice. IGF-1 silencing attenuated HG-induced podocyte injury, apoptosis and reduction in autophagy. Activating the JAK2/STAT signalling pathway or inhibiting autophagy reversed the effects of IGF-1 silencing on HG-treated MPC-5 cells. CONCLUSION: Knocking down IGF-1 alleviates HG-induced podocyte injury and apoptosis by inactivating the JAK2/STAT signalling pathway and enhancing autophagy.

13.
J Cell Sci ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587100

RESUMO

During development neurons achieve a stereotyped neuron type-specific morphology, which relies on dynamic support by microtubules (MTs). An important player is augmin which binds to existing MT filaments and recruits the γ-Tubulin Ring Complex (γ-TuRC), to form branched MTs. In cultured neurons, augmin is important for neurite formation. However, little is known about the role of augmin during neurite formation in vivo. Here, we have revisited the role of mammalian augmin in culture and then turned towards the class four Drosophila dendritic arborization (c4da) neurons. We show that MT density is maintained through augmin in cooperation with the γ-TuRC in vivo. Mutant c4da neurons show a reduction of newly emerging higher-order dendritic branches and in turn also a reduced number of their characteristic space-filling higher-order branchlets. Taken together, our data reveal a cooperative function of the augmin complex with the γ-TuRC in forming enough MTs needed for the appropriate differentiation of morphologically complex dendrites in vivo.

14.
Int J Mol Sci ; 25(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38612578

RESUMO

Ultraviolet radiation (UVR) has various effects on human cells and tissues, which can lead to a variety of skin diseases and cause inconvenience to people's lives. Among them, solar dermatitis is one of the important risk factors for malignant melanoma, so prevention and treatment of solar dermatitis is very necessary. Additionally, liquiritin (LQ) has anti-inflammatory effects. In this study, we aimed to evaluate the anti-inflammatory and pro-wound healing effects of liquiritin carbomer gel cold paste (LQ-CG-CP) in vitro and in vivo. The results of MTT experiments showed no cytotoxicity of LQ at concentrations of 40 µg/mL and below and cell damage at UVB irradiation doses above 60 mJ/cm2. Moreover, LQ can promote cell migration. ELISA results also showed that LQ inhibited the elevation of the inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) after UVB irradiation. In the mouse model of solar dermatitis, 2% LQ-CG-CP showed the best therapeutic efficacy for wound healing and relief of itching compared to MEIBAO moist burn moisturizer (MEBO). What is more, the results of skin histopathological examination show that LQ-CG-CP promotes re-epithelialization, shrinks wounds, and promotes collagen production, thus promoting wound healing. Simultaneously, LQ-CG-CP reduced TNF-α, IL-1ß, and IL-6 expression. In addition, LQ-CG-CP was not observed to cause histopathological changes and blood biochemical abnormalities in mice. Overall, LQ-CG-CP has great potential for the treatment of solar dermatitis.


Assuntos
Resinas Acrílicas , Dermatite , Flavanonas , Glucosídeos , Queimadura Solar , Animais , Camundongos , Humanos , Raios Ultravioleta , Interleucina-6 , Fator de Necrose Tumoral alfa , Cicatrização , Interleucina-1beta , Anti-Inflamatórios
15.
Nutrients ; 16(7)2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38612965

RESUMO

The lipid accumulation product (LAP) is a reliable marker of metabolic syndrome, which includes conditions like obesity. However, the correlation between the circulating selenium (CSe) concentration and the LAP is currently unclear. This study aimed to ascertain this correlation. Overall, 12,815 adults aged ≥20 years were enrolled in this study. After adjusting for all the confounding variables, CSe was positively correlated to the LAP (ß = 0.41; 95% confidence interval [CI]: 0.28, 0.54; p < 0.001). Compared with the lowest quartile of CSe, the highest quartile of CSe was positively related to the LAP (ß = 0.16; 95% CI: 0.12, 0.21; p < 0.001). Moreover, the correlation between CSe and the LAP revealed a positive non-linear trend. In the subgroup analysis, interaction effects were observed for age, sex, smoking, and stroke (p for interaction < 0.05). The effects were stronger for males (ß = 0.64, 95% CI: 0.47, 0.80; p < 0.001) and individuals who smoke at the time of the trial (ß = 0.64, 95% CI: 0.37, 0.91; p < 0.001). In conclusion, our results indicated that CSe was positively correlated with the LAP in a non-linear manner. Future research is warranted to explore their relationship and better understand the mechanisms underlying this association.


Assuntos
Produto da Acumulação Lipídica , Síndrome Metabólica , Selênio , Adulto , Masculino , Humanos , Estudos Transversais , Síndrome Metabólica/epidemiologia , Obesidade
16.
J Clin Nurs ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454556

RESUMO

AIMS AND OBJECTIVES: To assess the effectiveness of different nonpharmacological treatments for severe radiation-induced oral mucositis in patients with head and neck cancer. BACKGROUND: Radiation-induced oral mucositis is highly prevalent in patients with head and neck cancer. Current medications for radiation-induced oral mucositis are limited in effectiveness and susceptible to side effects, and while there is an increasing adoption of nonpharmacological interventions, the optimal one remains unclear. DESIGN: Systematic review and network meta-analysis based on the PRISMA-NMA guidelines. METHODS: Six databases were searched. Two authors independently performed the literature screening, data extraction and methodological quality assessment of the included studies. Traditional pairwise meta-analysis was performed by R Studio. A network meta-analysis was then conducted to assess the effects of nonpharmacological interventions for severe radiation-induced oral mucositis in patients with head and neck cancer. RESULTS: Fifty-two studies involving seven types of nonpharmacological interventions were enrolled. The network meta-analysis indicated that natural plant-based therapies might be the most effective, health education interventions might be the second most effective, and honey might be the third most effective interventions for reducing the incidence of severe radiation-induced oral mucositis. For reducing the incidence of severe oral mucositis-related pain, the pairwise meta-analysis showed that only natural plant-based therapies and health education interventions were effective. CONCLUSIONS: Nonpharmacological interventions are effective in the management of severe radiation-induced oral mucositis among patients with head and neck cancer. RELEVANCE TO CLINICAL PRACTICE: Nonpharmacological interventions are a category of safe and effective adjunctive therapies that should be encouraged in clinical practice. TRIAL REGISTRATION DETAILS: CRD42023400745.

17.
Cancer Res ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501978

RESUMO

Immune checkpoint inhibitors (ICI) have transformed cancer treatment. However, only a minority of patients achieve a profound response. Many patients are innately resistant while others acquire resistance to ICIs. Furthermore, hepatotoxicity and suboptimal efficacy have hampered the clinical development of agonists of 4-1BB, a promising immune stimulating target. To effectively target 4-1BB and treat diseases resistant to ICIs, we engineered ATG-101, a tetravalent "2+2" PD-L1×4-1BB bispecific antibody. ATG-101 bound PD-L1 and 4-1BB concurrently, with a greater affinity for PD-L1, and potently activated 4-1BB+ T cells when crosslinked with PD-L1+ cells. ATG-101 activated exhausted T cells upon PD-L1 binding, indicating a possible role in reversing T-cell dysfunction. ATG-101 displayed potent antitumor activity in numerous in vivo tumor models, including those resistant or refractory to ICIs. ATG-101 greatly increased the proliferation of CD8+ T cells, the infiltration of effector memory T cells, and the ratio of CD8+ T/Treg cells in the tumor microenvironment (TME), rendering an immunologically "cold" tumor "hot". Comprehensive characterization of the TME after ATG-101 treatment using single-cell RNA-sequencing further revealed an altered immune landscape that reflected increased antitumor immunity. ATG-101 was well-tolerated and did not induce hepatotoxicity in non-human primates. According to computational semi-mechanistic pharmacology modeling, 4-1BB/ATG-101/PD-L1 trimer formation and PD-L1 receptor occupancy were both maximized at around 2 mg/kg of ATG-101, providing guidance regarding the optimal biological dose for clinical trials. In summary, by localizing to PD-L1-rich microenvironments and activating 4-1BB+ immune cells in a PD-L1 crosslinking-dependent manner, ATG-101 safely inhibits growth of ICI resistant and refractory tumors.

18.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(3): 273-278, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38512038

RESUMO

Natural killer (NK) cells directly lysis the virus-infected cells through rapidly releasing cytotoxic mediators and cytokines. The balance between inhibitory and activated receptors on the surface of NK cells, as well as the corresponding ligands expressed on target cells are involved in the regulation of the cytotoxic function of NK cells. NKG2A is one of the highly anticipated inhibitory receptors expressed on NK cells, which can inhibit the cytotoxicity of NK cells to autologous normal tissue cells through interacting with the ligand HLA-E. The studies have shown that HLA-E is overexpressed on virus-infected cells and forms a complex with peptides derived from viral proteins. The interaction of HLA-E and NKG2A can regulate the functions of NK cells, participateing the pathogenesis process of virus infectious diseases. This review outlines the characteristics of the molecular interaction between NKG2A and HLA-E, as well as the mechanisms of NKG2A-HLA-E axis in regulating NK cell responses.


Assuntos
Doenças Transmissíveis , 60617 , Humanos , Células Matadoras Naturais , Citocinas
19.
Neuron ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38513667

RESUMO

Neuronal loss is the central issue in Alzheimer's disease (AD), yet no treatment developed so far can halt AD-associated neurodegeneration. Here, we developed a monoclonal antibody (mAb2A7) against 217 site-phosphorylated human tau (p-tau217) and observed that p-tau217 levels positively correlated with brain atrophy and cognitive impairment in AD patients. Intranasal administration efficiently delivered mAb2A7 into male PS19 tauopathic mouse brain with target engagement and reduced tau pathology/aggregation with little effect on total soluble tau. Further, mAb2A7 treatment blocked apoptosis-associated neuronal loss and brain atrophy, reversed cognitive deficits, and improved motor function in male tauopathic mice. Proteomic analysis revealed that mAb2A7 treatment reversed alterations mainly in proteins associated with synaptic functions observed in murine tauopathy and AD brain. An antibody (13G4) targeting total tau also attenuated tau-associated pathology and neurodegeneration but impaired the motor function of male tauopathic mice. These results implicate p-tau217 as a potential therapeutic target for AD-associated neurodegeneration.

20.
Sci Rep ; 14(1): 6655, 2024 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509147

RESUMO

Tripartite motif-containing protein 7 (TRIM7), as an E3 ligase, plays an important regulatory role in various physiological and pathological processes. However, the role of TRIM7 in gastric cancer (GC) is still undefined. Our study detected the expression of TRIM7 in clinical specimens and investigated the regulatory effect and molecular mechanism of TRIM7 on GC progression through in vitro and in vivo experiments. Our finding showed that TRIM7 was significantly downregulated in GC, and patients with high expression of TRIM7 showed long overall survival. Both in vitro and in vivo experiments showed that TRIM7 dramatically suppressed the malignant progression of GC. Further investigation showed that ferroptosis was the major death type mediated by TRIM7. Mechanistically, TRIM7 interacted with SLC7A11 through its B30.2/SPRY domain and promoted Lys48-linked polyubiquitination of SLC7A11, which effectively suppressing SLC7A11/GPX4 axis and inducing ferroptosis in GC cells. In vivo experiments and correlation analysis based on clinical specimens further confirmed that TRIM7 inhibited tumor growth through suppressing SLC7A11/GPX4 axis. In conclusion, our investigation demonstrated for the first time that TRIM7, as a tumor suppressor, induced ferroptosis via targeting SLC7A11 in GC, which provided a new strategy for the molecular therapy of GC by upregulating TRIM7.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Ubiquitina-Proteína Ligases/genética , Transformação Celular Neoplásica , Carcinogênese , Ubiquitinação , Sistema y+ de Transporte de Aminoácidos/genética , Proteínas com Motivo Tripartido/genética
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