Cell Biology and Toxicology最新文献_第4页

Metal ions overloading and cell death. 金属离子超载与细胞死亡

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-08-20 DOI: 10.1007/s10565-024-09910-4

Yun Lai, Fen Fen Gao, Ruo Ting Ge, Rui Liu, Shumei Ma, Xiaodong Liu

{"title":"Metal ions overloading and cell death.","authors":"Yun Lai, Fen Fen Gao, Ruo Ting Ge, Rui Liu, Shumei Ma, Xiaodong Liu","doi":"10.1007/s10565-024-09910-4","DOIUrl":"10.1007/s10565-024-09910-4","url":null,"abstract":"Cell death maintains cell morphology and homeostasis during development by removing damaged or obsolete cells. The concentration of metal ions whithin cells is regulated by various intracellular transporters and repositories to maintain dynamic balance. External or internal stimuli might increase the concentration of metal ions, which results in ions overloading. Abnormal accumulation of large amounts of metal ions can lead to disruption of various signaling in the cell, which in turn can produce toxic effects and lead to the occurrence of different types of cell deaths. In order to further study the occurrence and development of metal ions overloading induced cell death, this paper reviewed the regulation of Ca2+, Fe3+, Cu2+ and Zn2+ metal ions, and the internal mechanism of cell death induced by overloading. Furthermore, we found that different metal ions possess a synergistic and competitive relationship in the regulation of cell death. And the enhanced level of oxidative stress was present in all the processes of cell death due to metal ions overloading, which possibly due to the combination of factors. Therefore, this review offers a theoretical foundation for the investigation of the toxic effects of metal ions, and presents innovative insights for targeted regulation and therapeutic intervention. HIGHLIGHTS: • Metal ions overloading disrupts homeostasis, which in turn affects the regulation of cell death. • Metal ions overloading can cause cell death via reactive oxygen species (ROS). • Different metal ions have synergistic and competitive relationships for regulating cell death.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"72"},"PeriodicalIF":5.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cocaine-derived hippuric acid activates mtDNA-STING signaling in alcoholic liver disease: Implications for alcohol and cocaine co-abuse. 可卡因衍生的马尿酸可激活酒精性肝病中的mtDNA-STING信号转导：对酒精和可卡因共同滥用的影响。

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-08-16 DOI: 10.1007/s10565-024-09901-5

Hwan Ma, Gyu-Rim Lee, Jeong-Su Park, Jin Lee, Feng Wang, Yuanqiang Ma, Guo-Yan Sui, Nodir Rustamov, Sou Hyun Kim, Young-Suk Jung, Hwan-Soo Yoo, Sang-Bae Han, Jin Tae Hong, Jaesuk Yun, Yoon Seok Roh

{"title":"Cocaine-derived hippuric acid activates mtDNA-STING signaling in alcoholic liver disease: Implications for alcohol and cocaine co-abuse.","authors":"Hwan Ma, Gyu-Rim Lee, Jeong-Su Park, Jin Lee, Feng Wang, Yuanqiang Ma, Guo-Yan Sui, Nodir Rustamov, Sou Hyun Kim, Young-Suk Jung, Hwan-Soo Yoo, Sang-Bae Han, Jin Tae Hong, Jaesuk Yun, Yoon Seok Roh","doi":"10.1007/s10565-024-09901-5","DOIUrl":"10.1007/s10565-024-09901-5","url":null,"abstract":"The simultaneous abuse of alcohol-cocaine is known to cause stronger and more unpredictable cellular damage in the liver, heart, and brain. However, the mechanistic crosstalk between cocaine and alcohol in liver injury remains unclear. The findings revealed cocaine-induced liver injury and inflammation in both marmosets and mice. Of note, co-administration of cocaine and ethanol in mice causes more severe liver damage than individual treatment. The metabolomic analysis confirmed that hippuric acid (HA) is the most abundant metabolite in marmoset serum after cocaine consumption and that is formed in primary marmoset hepatocytes. HA, a metabolite of cocaine, increases mitochondrial DNA leakage and subsequently increases the production of proinflammatory factors via STING signaling in Kupffer cells (KCs). In addition, conditioned media of cocaine-treated KC induced hepatocellular necrosis via alcohol-induced TNFR1. Finally, disruption of STING signaling in vivo ameliorated co-administration of alcohol- and cocaine-induced liver damage and inflammation. These findings postulate intervention of HA-STING-TNFR1 axis as a novel strategy for treatment of alcohol- and cocaine-induced excessive liver damage.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"71"},"PeriodicalIF":5.3,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11327214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mesenchymal stem cell-based therapy for paraquat-induced lung injury. 基于间充质干细胞的百草枯肺损伤疗法。

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-08-13 DOI: 10.1007/s10565-024-09911-3

Xiaping Zhang, Ting Li, Yuan-Qiang Lu

{"title":"Mesenchymal stem cell-based therapy for paraquat-induced lung injury.","authors":"Xiaping Zhang, Ting Li, Yuan-Qiang Lu","doi":"10.1007/s10565-024-09911-3","DOIUrl":"10.1007/s10565-024-09911-3","url":null,"abstract":"Paraquat poisoning results in significant pulmonary damage, but current treatments are only minimally effective in repairing the injured lung tissues. Recent research has highlighted the promise of using stem cell therapy, namely mesenchymal stem cells, as a new method for treating paraquat toxicity. These cells have shown effectiveness in decreasing inflammation, apoptosis, and fibrosis in the mice lungs subjected to paraquat. The therapeutic implications of mesenchymal stem cells are believed to arise from their release of bioactive proteins and their capacity to regulate inflammatory responses. However, additional clinical study is required to validate these therapies' efficacy. This review thoroughly explores the pathophysiology of paraquat poisoning and the properties of mesenchymal stem cells. Additionally, it critically assesses the long-term safety and effectiveness of mesenchymal stem cell therapies, which is crucial for developing more dependable and effective treatment protocols. In summary, although mesenchymal stem cells offer promising prospects for treating lung injuries, more investigations are required to optimize their therapeutic promise and ensure their safe clinical application in the context of paraquat poisoning.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"70"},"PeriodicalIF":5.3,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11322247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Screening persistent organic pollutants for effects on testosterone and estrogen synthesis at human-relevant concentrations using H295R cells in 96-well plates. 使用 96 孔板中的 H295R 细胞筛选持久性有机污染物对人体相关浓度下睾酮和雌激素合成的影响。

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-08-13 DOI: 10.1007/s10565-024-09902-4

Denise Strand, Erik Nylander, Andrey Höglund, Bo Lundgren, Jonathan W Martin, Oskar Karlsson

{"title":"Screening persistent organic pollutants for effects on testosterone and estrogen synthesis at human-relevant concentrations using H295R cells in 96-well plates.","authors":"Denise Strand, Erik Nylander, Andrey Höglund, Bo Lundgren, Jonathan W Martin, Oskar Karlsson","doi":"10.1007/s10565-024-09902-4","DOIUrl":"10.1007/s10565-024-09902-4","url":null,"abstract":"Many persistent organic pollutants (POPs) are suspected endocrine disruptors and it is important to investigate their effects at low concentrations relevant to human exposure. Here, the OECD test guideline #456 steroidogenesis assay was downscaled to a 96-well microplate format to screen 24 POPs for their effects on viability, and testosterone and estradiol synthesis using the human adrenocortical cell line H295R. The compounds (six polyfluoroalkyl substances, five organochlorine pesticides, ten polychlorinated biphenyls and three polybrominated diphenyl ethers) were tested at human-relevant levels (1 nM to 10 µM). Increased estradiol synthesis, above the OECD guideline threshold of 1.5-fold solvent control, was shown after exposure to 10 µM PCB-156 (153%) and PCB-180 (196%). Interestingly, the base hormone synthesis varied depending on the cell batch. An alternative data analysis using a linear mixed-effects model that include multiple independent experiments and considers batch-dependent variation was therefore applied. This approach revealed small but statistically significant effects on estradiol or testosterone synthesis for 17 compounds. Increased testosterone levels were demonstrated even at 1 nM for PCB-74 (18%), PCB-99 (29%), PCB-118 (16%), PCB-138 (19%), PCB-180 (22%), and PBDE-153 (21%). The MTT assay revealed significant effects on cell viability after exposure to 1 nM of perfluoroundecanoic acid (12%), 3 nM PBDE-153 (9%), and 10 µM of PCB-156 (6%). This shows that some POPs can interfere with endocrine signaling at concentrations found in human blood, highlighting the need for further investigation into the toxicological mechanisms of POPs and their mixtures at low concentrations relevant to human exposure.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"69"},"PeriodicalIF":5.3,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11322491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to: Urinary extracellular vesicles prevent di-(2-ethylhexyl) phthalate-induced hypospadias by facilitating epithelial-mesenchymal transition via PFN2 delivery. 更正：尿液细胞外囊泡通过 PFN2 递送促进上皮-间质转化，防止邻苯二甲酸二（2-乙基己基）酯诱发尿道下裂。

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-08-12 DOI: 10.1007/s10565-024-09898-x

Shibo Zhu, Xiangliang Tang, Jin Zhang, Jinhua Hu, Xiaofeng Gao, Dian Li, Wei Jia

引用次数: 0

Antitumorigenic potential of Lactobacillus-derived extracellular vesicles: p53 succinylation and glycolytic reprogramming in intestinal epithelial cells via SIRT5 modulation. 源于乳酸杆菌的细胞外囊泡的抗肿瘤潜力：通过 SIRT5 调节肠上皮细胞中的 p53 succinylation 和糖酵解重编程。

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-08-07 DOI: 10.1007/s10565-024-09897-y

Jingbo Zhang, Xiumei Huang, Tingting Zhang, Chongqi Gu, Wei Zuo, Lijuan Fu, Yiping Dong, Hao Liu

{"title":"Antitumorigenic potential of Lactobacillus-derived extracellular vesicles: p53 succinylation and glycolytic reprogramming in intestinal epithelial cells via SIRT5 modulation.","authors":"Jingbo Zhang, Xiumei Huang, Tingting Zhang, Chongqi Gu, Wei Zuo, Lijuan Fu, Yiping Dong, Hao Liu","doi":"10.1007/s10565-024-09897-y","DOIUrl":"10.1007/s10565-024-09897-y","url":null,"abstract":"Objective: Colorectal cancer progression involves complex cellular mechanisms. This study examines the effects of Lactobacillus plantarum-derived extracellular vesicles (LEVs) on the SIRT5/p53 axis, focusing on glycolytic metabolic reprogramming and abnormal proliferation in intestinal epithelial cells.Methods: LEVs were isolated from Lactobacillus plantarum and incubated with Caco-2 cells. Differential gene expression was analyzed through RNA sequencing and compared with TCGA-COAD data. Key target genes and pathways were identified using PPI network and pathway enrichment analysis. Various assays, including RT-qPCR, EdU staining, colony formation, flow cytometry, and Western blotting, were used to assess gene expression, cell proliferation, and metabolic changes. Co-immunoprecipitation confirmed the interaction between SIRT5 and p53, and animal models were employed to validate in vivo effects.Results: Bioinformatics analysis indicated the SIRT5/p53 axis as a critical pathway in LEVs' modulation of colorectal cancer. LEVs were found to inhibit colorectal cancer cell proliferation and glycolytic metabolism by downregulating SIRT5, influencing p53 desuccinylation. In vivo, LEVs regulated this axis, reducing tumor formation in mice. Clinical sample analysis showed that SIRT5 and p53 succinylation levels correlated with patient prognosis.Conclusion: Lactobacillus-derived extracellular vesicles play a pivotal role in suppressing colonic tumor formation by modulating the SIRT5/p53 axis. This results in decreased glycolytic metabolic reprogramming and reduced proliferation in intestinal epithelial cells.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"66"},"PeriodicalIF":5.3,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biomedical application of TiO₂NPs can cause arterial thrombotic risks through triggering procoagulant activity, activation and aggregation of platelets. TiO2NPs 的生物医学应用可通过触发促凝血活性、激活和聚集血小板而导致动脉血栓风险。

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-08-07 DOI: 10.1007/s10565-024-09908-y

Yiying Bian, Qiushuo Jin, Jinrui He, Thien Ngo, Ok-Nam Bae, Liguo Xing, Jingbo Pi, Han Young Chung, Yuanyuan Xu

{"title":"Biomedical application of TiO2NPs can cause arterial thrombotic risks through triggering procoagulant activity, activation and aggregation of platelets.","authors":"Yiying Bian, Qiushuo Jin, Jinrui He, Thien Ngo, Ok-Nam Bae, Liguo Xing, Jingbo Pi, Han Young Chung, Yuanyuan Xu","doi":"10.1007/s10565-024-09908-y","DOIUrl":"10.1007/s10565-024-09908-y","url":null,"abstract":"Background: Titanium dioxide nanoparticles (TiO2NPs) are widely used in medical application. However, the relevant health risk has not been completely assessed, the potential of inducing arterial thrombosis (AT) in particular.Methods: Alterations in platelet function and susceptibility to arterial thrombosis induced by TiO2NPs were examined using peripheral blood samples from healthy adult males and an in vivo mouse model, respectively.Results: Here, using human platelets (hPLTs) freshly isolated from health volunteers, we demonstrated TiO2NP treatment triggered the procoagulant activity of hPLTs through phosphatidylserine exposure and microvesicles generation. In addition, TiO2NP treatment increased the levels of glycoprotein IIb/IIIa and P-selectin leading to aggregation and activation of hPLTs, which were exacerbated by providing physiology-mimicking conditions, including introduction of thrombin, collagen, and high shear stress. Interestingly, intracellular calcium levels in hPLTs were increased upon TiO2NP treatment, which were crucial in TiO2NP-induced hPLT procoagulant activity, activation and aggregation. Moreover, using mice in vivo models, we further confirmed that TiO2NP treatment a reduction in mouse platelet (mPLT) counts, disrupted blood flow, and exacerbated carotid arterial thrombosis with enhanced deposition of mPLT.Conclusions: Together, our study provides evidence for an ignored health risk caused by TiO2NPs, specifically TiO2NP treatment augments procoagulant activity, activation and aggregation of PLTs via calcium-dependent mechanism and thus increases the risk of AT.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"67"},"PeriodicalIF":5.3,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unraveling the molecular complexity: Wtap/Ythdf1 and Lcn2 in novel traumatic brain injury secondary injury mechanisms. 揭示分子复杂性：新型创伤性脑损伤继发性损伤机制中的 Wtap/Ythdf1 和 Lcn2。

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-08-07 DOI: 10.1007/s10565-024-09909-x

Chaobang Ma, Caili Gou, Shiyu Sun, Junmin Wang, Xin Wei, Fei Xing, Na Xing, Jingjing Yuan, Zhongyu Wang

{"title":"Unraveling the molecular complexity: Wtap/Ythdf1 and Lcn2 in novel traumatic brain injury secondary injury mechanisms.","authors":"Chaobang Ma, Caili Gou, Shiyu Sun, Junmin Wang, Xin Wei, Fei Xing, Na Xing, Jingjing Yuan, Zhongyu Wang","doi":"10.1007/s10565-024-09909-x","DOIUrl":"10.1007/s10565-024-09909-x","url":null,"abstract":"The primary aim of this research was to explore the functions of Wtap and Ythdf1 in regulating neuronal Lipocalin-2 (Lcn2) through m6A modification in traumatic brain injury (TBI). By employing transcriptome sequencing and enrichment analysis, we identified the Wtap/Ythdf1-mediated Lcn2 m6A modification pathway as crucial in TBI. In our in vitro experiments using primary cortical neurons, knockout of Wtap and Ythdf1 led to the inhibition of Lcn2 m6A modification, resulting in reduced neuronal death and inflammation. Furthermore, overexpression of Lcn2 in cortical neurons induced the activation of reactive astrocytes and M1-like microglial cells, causing neuronal apoptosis. In vivo experiments confirmed the activation of reactive astrocytes and microglial cells in TBI and importantly demonstrated that Wtap knockdown improved neuroinflammation and functional impairment. These findings underscore the significance of Wtap/Ythdf1-mediated Lcn2 regulation in TBI secondary injury and suggest potential therapeutic implications for combating TBI-induced neuroinflammation and neuronal damage.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"65"},"PeriodicalIF":5.3,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel therapeutic targets: bifidobacterium-mediated urea cycle regulation in colorectal cancer 新的治疗目标：双歧杆菌介导的结直肠癌尿素循环调节

IF 6.1 2区医学

Cell Biology and Toxicology Pub Date : 2024-08-03 DOI: 10.1007/s10565-024-09889-y

Xusheng Nie, Tingting Zhang, Xiumei Huang, Chongqi Gu, Wei Zuo, Li-Juan Fu, Yiping Dong, Hao Liu

{"title":"Novel therapeutic targets: bifidobacterium-mediated urea cycle regulation in colorectal cancer","authors":"Xusheng Nie, Tingting Zhang, Xiumei Huang, Chongqi Gu, Wei Zuo, Li-Juan Fu, Yiping Dong, Hao Liu","doi":"10.1007/s10565-024-09889-y","DOIUrl":"https://doi.org/10.1007/s10565-024-09889-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background and purpose</h3>Colorectal cancer (CRC) is a widespread malignancy with a complex and not entirely elucidated pathogenesis. This study aims to explore the role of Bifidobacterium in the urea cycle (UC) and its influence on the progression of CRC, a topic not extensively studied previously.<h3 data-test=\"abstract-sub-heading\">Experimental approach</h3>Utilizing both bioinformatics and experimental methodologies, this research involved analyzing bacterial abundance in CRC patients in comparison to healthy individuals. The study particularly focused on the abundance of BA. Additionally, transcriptomic data analysis and cellular experiments were conducted to investigate the impact of Bifidobacterium on ammonia metabolism and mitochondrial function, specifically examining its regulation of the key UC gene, ALB.<h3 data-test=\"abstract-sub-heading\">Key results</h3>The analysis revealed a significant decrease in Bifidobacterium abundance in CRC patients. Furthermore, Bifidobacterium was found to suppress ammonia metabolism and induce mitochondrial dysfunction through the regulation of the ALB gene, which is essential in the context of UC. These impacts contributed to the suppression of CRC cell proliferation, a finding corroborated by animal experimental results.<h3 data-test=\"abstract-sub-heading\">Conclusions and implications</h3>This study elucidates the molecular mechanism by which Bifidobacterium impacts CRC progression, highlighting its role in regulating key metabolic pathways. These findings provide potential targets for novel therapeutic strategies in CRC treatment, emphasizing the importance of microbiota in cancer progression.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"54 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141884099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FOXC1 transcriptionally suppresses ABHD5 to inhibit the progression of renal cell carcinoma through AMPK/mTOR pathway. FOXC1通过AMPK/mTOR途径转录抑制ABHD5，从而抑制肾细胞癌的进展。

IF 5.3 2区医学

Cell Biology and Toxicology Pub Date : 2024-08-02 DOI: 10.1007/s10565-024-09899-w

Jianfa Li, Shuangchen Chen, Jing Xiao, Jiayuan Ji, Chenchen Huang, Ge Shu

{"title":"FOXC1 transcriptionally suppresses ABHD5 to inhibit the progression of renal cell carcinoma through AMPK/mTOR pathway.","authors":"Jianfa Li, Shuangchen Chen, Jing Xiao, Jiayuan Ji, Chenchen Huang, Ge Shu","doi":"10.1007/s10565-024-09899-w","DOIUrl":"10.1007/s10565-024-09899-w","url":null,"abstract":"Background: Increased activity of the transcription factor FOXC1 leads to elevated transcription of target genes, ultimately facilitating the progression of various cancer types. However, there are currently no literature reports on the role of FOXC1 in renal cell carcinoma.Methods: By using RT-qPCR, immunohistochemistry and Western blotting, FOXC1 mRNA and protein expression was evaluated. Gain of function experiments were utilized to assess the proliferation and metastasis ability of cells. A nude mouse model was created for transplanting tumors and establishing a lung metastasis model to observe cell proliferation and spread in a living organism. Various techniques including biological analysis, CHIP assay, luciferase assay, RT-qRCR and Western blotting experiments were utilized to investigate how FOXC1 contributes to the transcription of ABHD5 on a molecular level. FOXC1 was assessed by Western blot for its impact on AMPK/mTOR signaling pathway.Results: FOXC1 is down-regulated in RCC, causing unfavorable prognosis of patients with RCC. Further experiments showed that forced FOXC1 expression significantly restrains RCC cell growth and cell metastasis. Mechanically, FOXC1 promotes the transcription of ABHD5 to activate AMPK signal pathway to inhibit mTOR signal pathway. Finally, knockdown of ABHD5 recovered the inhibitory role of FOXC1 overexpression induced cell growth and metastasis suppression.Conclusion: In general, our study demonstrates that FOXC1 exerts its tumor suppressor role by promoting ABHD5 transcription to regulating AMPK/mTOR signal pathway. FOXC1 could serve as both a diagnostic indicator and potential treatment focus for RCC.","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"40 1","pages":"62"},"PeriodicalIF":5.3,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0