Oncology Research最新文献

{"title":"The impact of oxidative stress and the NRF2-KEAP1-ARE signaling pathway on anticancer drug resistance.","authors":"FLáVIA Alves Verza, Guilherme Carvalho DA Silva, Felipe Garcia Nishimura","doi":"10.32604/or.2025.065755","DOIUrl":"10.32604/or.2025.065755","url":null,"abstract":"<p><p>Cancer remains a major global health burden, with rising incidence and mortality linked to aging populations and increased exposure to genotoxic agents. Oxidative stress plays a critical role in cancer development, progression, and resistance to therapy. The nuclear factor erythroid 2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1)-antioxidant response element (ARE) signaling pathway is central to maintaining redox balance by regulating the expression of antioxidant and detoxification genes. Under physiological conditions, this pathway protects cells from oxidative damage, however, sustained activation of NRF2 in cancer, often due to mutations in KEAP1, supports tumor cell survival, drug resistance, and metabolic reprogramming. Recent studies demonstrate that NRF2 enhances glutathione (GSH) synthesis, induces detoxifying enzymes, and upregulates drug efflux transporters, collectively contributing to resistance against chemotherapy and targeted therapies. The inhibition of NRF2 using small molecules or dietary phytochemicals has shown promise in restoring drug sensitivity in preclinical cancer models. This review highlights the dual role of NRF2 in redox regulation and cancer therapy, emphasizing its potential as a therapeutic target. While targeting NRF2 offers a novel approach to overcoming treatment resistance, further research is needed to enhance specificity and facilitate clinical translation.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 8","pages":"1819-1834"},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3-O-Acetyl-11-Keto-<b>β</b>-Boswellic Acid Suppresses Colitis-Associated Colorectal Cancer by Inhibiting the NF-Kb Signaling Pathway and Remodeling Gut Microbiota.","authors":"Fang Xu, Wan Li, Xiang-Jin Zheng, Yue Hao, Yi-Hui Yang, Hong Yang, Sen Zhang, Wan-Xin Cao, Xiao-Xue Li, Xu Zhang, Guan-Hua Du, Teng-Fei Ji, Jin-Hua Wang","doi":"10.32604/or.2025.062386","DOIUrl":"10.32604/or.2025.062386","url":null,"abstract":"<p><strong>Objectives: </strong>Colorectal cancer (CRC) is one of the most common cancers all over the world. The progression of CRC is associated with inflammation and disruptions in intestinal flora. 3-O-Acetyl-11-keto-β-boswellic acid (AKBA) has been noted for its potent anti-inflammatory properties. However, the effect of AKBA on colon cancer caused by inflammation and its mechanism are not unclear. The study is to explore the effect of AKBA on CRC and its mechanism.</p><p><strong>Materials and methods: </strong>Cell proliferation, (5-ethynyl-2^'-deoxyuridine, EdU)-DNA synthesis assay and colony formation were used to assess the effect of AKBA on the proliferation of CRC cells. Flow cytometry was employed to analyze the cell cycle and apoptosis rate of cells treated with AKBA. RNA sequencing was done to explore the underlying mechanisms of AKBA. Western blot was used to assess the expression of key proteins in the nuclear factor kappa-B (NF-κB) signaling pathway after the treatment of AKBA. Real-time quantitative PCR (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and Meso Scale Discovery (MSD) assays were employed to check the anti-inflammation effects of AKBA on Lipopolysaccharide (LPS)-induced RAW264.7 cells and LPS-induced mouse model. Additionally, the Azoxymethane/Dextran sulfate sodium (AOM/DSS)-induced colitis-associated CRC model was used to evaluate the anti-CRC effect of AKBA. Gut microbiota profiling of fecal samples from CRC mice, both with and without AKBA treatment, was conducted through metagenomic sequencing analysis.</p><p><strong>Results: </strong>Our results showed that AKBA reduced the proliferation of HCT116 and SW620 cells, increased apoptosis of cells, and arrested the cell cycle at the G2/M phase. Results from RNA-seq showed that AKBA inhibited CRC by inhibiting the NF-κB signaling pathway and reducing cellular inflammation. Furthermore, AKBA reduced the levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), Interferon-γ (IFN-γ), Interleukin-IL-12p70 (IL-12p70), Interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in both the spleen and serum of LPS-induced acute inflammation mice. Additionally, AKBA inhibited the development of AOM/DSS-induced colitis-associated colon cancer in mice and positively influenced gut microbiota.</p><p><strong>Conclusion: </strong>This study highlights the inhibitory effect of AKBA on colitis-associated CRC and reveals a novel aspect of its role in the remodeling of gut microbiota. These findings suggest that AKBA may be used as a potential therapeutic agent for CRC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 8","pages":"1969-1989"},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP13 Suppresses Colorectal Cancer Angiogenesis by Downregulating VEGFA Expression through Inhibition of the PTEN-AKT Pathway.","authors":"Guo-Zhi Xu, Han-Yang Guan, Yan-Guan Guo, Yi-Ran Zhang, Jing-Hua Pan, Simin Luo, Hui Ding, Yunlong Pan, Qi Yao","doi":"10.32604/or.2025.060440","DOIUrl":"10.32604/or.2025.060440","url":null,"abstract":"<p><strong>Background: </strong>Tumor angiogenesis is related to solid tumor occurrence. Ubiquitin-specific peptidase 13 (USP13) is a deubiquitinating enzyme with a pivotal effect on tumor proliferation, metastasis, and tumorigenesis. Nonetheless, its effect on colorectal cancer (CRC) angiogenesis remains poorly understood.</p><p><strong>Methods: </strong>Human umbilical vein endothelial cells (HUVECs) and CRC cells were cultivated, followed by USP13 knockdown/overexpression using shRNA lentiviral vectors or plasmids. Conditioned media (CM) from treated CRC cells were collected to assess HUVEC migration, invasion, and tube formation. Phosphatase and tensin homolog (PTEN) overexpression and recombinant vascular endothelial growth factor A (VEGFA) rescue experiments were performed. Molecular mechanisms were analyzed via Western blot (PTEN, p-AKT, VEGFA), co-immunoprecipitation (PTEN ubiquitination), and <i>in vivo</i> nude mice study to detect the role of USP13 in tumor angiogenesis.</p><p><strong>Results: </strong>USP13 expression in CRC cells is downregulated and negatively related to platelet endothelial cell adhesion molecule-1 (CD31) expression. Furthermore, the conditioned medium from CRC cells with USP13 knockdown significantly promoted HUVEC migration, invasion, and tube formation, while USP13 overexpression exerted the opposite effect. Additionally, USP13 overexpression significantly increased PTEN expression while decreasing protein kinase B (AKT) phosphorylation levels. Concurrently, USP13 overexpression significantly reduced PTEN ubiquitination, whereas USP13 knockdown remarkably increased this modification. Overexpression of PTEN in sh-USP13 CRC cells decreased the expression levels of VEGFA and p-AKT. USP13 also inhibited tumor angiogenesis through downregulating VEGFA, and recombinant VEGFA blocked the inhibition of the conditioned medium from USP13-overexpressing CRC cells against HUVEC angiogenesis <i>in vivo</i>.</p><p><strong>Conclusions: </strong>USP13 downregulated VEGFA and inhibited tumor angiogenesis via the PTEN-AKT pathway.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 8","pages":"1947-1967"},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial pyruvate dehydrogenase phosphatase metabolism disorder in malignant tumors.","authors":"Yufeng Wang, Huifeng Dang, Qianqian Wang, Shuxiao Wu, Lei Han, X U Luo, Yingxia Tian, Hailin Tang","doi":"10.32604/or.2025.063716","DOIUrl":"10.32604/or.2025.063716","url":null,"abstract":"<p><p>This review focuses on the metabolic issues related to mitochondrial pyruvate dehydrogenase phosphatase (PDP) in malignant tumors and its potential mechanisms. Recent research on tumor metabolic mechanisms has shown that PDP dysregulation is closely linked to metabolic reprogramming in tumor cells, and potentially promotes tumor. Research has comprehensively explored the structural-functional characteristics of PDP, its metabolic regulatory mechanisms, and its role in various types of malignant tumors. Nevertheless, several questions still exist regarding its potential mechanisms within acetylation, phosphorylation, hypoxia, immune infiltration, mitochondrial metabolism, drug resistance, oxidative phosphorylation, and tumor prognosis. This article intends to summarize the latest research, examine PDP's potential as a therapeutic target, and propose future research directions to enhance cancer treatment strategies.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 8","pages":"1861-1874"},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: Inhibition of Liver Carcinoma Cell Invasion and Metastasis by Knockdown of Cullin7 <i>In Vitro</i> and <i>In Vivo</i>.","authors":"","doi":"10.32604/or.2025.070134","DOIUrl":"https://doi.org/10.32604/or.2025.070134","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3727/096504016X14519995067562.].</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 8","pages":"2179"},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying ATP-Binding Cassette Member B5 as a New Biomarker for Oral Squamous Cell Carcinoma.","authors":"Li Yu, Xiaoyan Zhang, Yan Feng, Xinyue Liao, Tiejun Zhou, Hang Si, Yun Feng, Decai Wang, Yongxian Lai","doi":"10.32604/or.2025.064276","DOIUrl":"10.32604/or.2025.064276","url":null,"abstract":"<p><strong>Background: </strong>Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy with a low five-year survival rate. ATP-binding cassette subfamily B member 5 (ABCB5) has been linked to tumorigenesis. However, its role in inducing OSCC remains unclear.</p><p><strong>Methods: </strong>Quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot, and immunocytochemistry (ICC) were performed to examine the level of ABCB5 in OSCC (CAL27 and HSC-3) and human oral keratinocyte (HOK). ABCB5 was knocked down in CAL27 cells using ABCB5-specific small interfering RNA (ABCB5 siRNA), and its contribution to migration, invasion, and epithelial-mesenchymal transition (EMT), a process by which epithelial cells lose their tight junction and acquire an increased migratory and invasive phenotype resembling that of mesenchymal cells, were evaluated by three-dimension and transwell migration and invasion assays, qRT-PCR and ICC. An <i>in vivo</i> OSCC model was established using 4-nitroquinoline-1-oxide (4NQO), a carcinogenic chemical that is commonly used to develop OSCC by destroying DNA synthesis and oxidative stress. Pathological alterations, ABCB5, and EMT markers were evaluated by H&E staining, immunohistochemistry, and qRT-PCR.</p><p><strong>Results: </strong>ABCB5 was significantly upregulated in CAL27 and HSC-3 cells as compared to HOK. Knockdown of ABCB5 significantly reduced the number of migrated and invaded CAL27 cells, accompanied by the significantly increased E-cadherin and decreased Vimentin and N-cadherin under Transforming growth factor β (TGF-β) treatment. <i>In vivo</i>, as OSCC advanced, a notable rise in the expressions of ABCB5, N-cadherin, and Vimentin, while a statistical decrease in E-cadherin was demonstrated.</p><p><strong>Conclusion: </strong>ABCB5 promotes the migration, invasion, and EMT of OSCC. ABCB5 might be a new biomarker and potential therapeutic target for OSCC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 8","pages":"2037-2053"},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VPS37A Activates the Autophagy-Lysosomal Pathway for TNFR1 Degradation and Induces NF-<b>κ</b>B-Regulated Cell Death under Metabolic Stress in Colorectal Cancer.","authors":"Chuncheng Liu, Xiaohan Liu, Ziqi Li, Yanruoxue Wei, Bangdong Liu, Peng Zhu, Yukun Liu, Ran Zhao","doi":"10.32604/or.2025.065739","DOIUrl":"10.32604/or.2025.065739","url":null,"abstract":"<p><strong>Background: </strong>VPS37A (VPS37A subunit of ESCRT-I), a component of the ESCRT-I (endosomal sorting complex required for transport I) complex, mediates vesicular trafficking through sorting endocytic ubiquitinated cargos into multivesicular bodies (MVBs). Although accumulating evidence indicates that VPS37A deficiency occurs in numerous malignancies and exerts tumor-suppressive effects during cancer progression, its functional significance in colorectal cancer (CRC) pathogenesis remains poorly characterized. Therefore, this study aims to further investigate the functional and molecular mechanisms by which VPS37A downregulation contributes to malignant biological phenotypes in CRC, with a specific focus on how its dysregulation affects cell death pathways.</p><p><strong>Methods: </strong>Multi-omics analysis of TCGA, GEO, and CPTAC cohorts identified VPS37A as a downregulated tumor suppressor gene in CRC. The prognostic relevance of VPS37A was validated in two clinical cohorts (Cohorts 1 and 2) using immunohistochemistry. Functional assays in VPS37A-overexpressing CRC cells and xenografts assessed proliferation, cell cycle progression, and stress-induced cell death. RNA sequencing, nuclear factor kappa-B (NF-κB) luciferase reporter assays, and lysosomal inhibition experiments elucidated the mechanisms underlying tumor necrosis factor receptor 1 (TNFR1) degradation.</p><p><strong>Results: </strong>VPS37A is significantly downregulated in advanced-stage CRC and independently predicts poor survival. Functionally, VPS37A overexpression suppresses proliferation and induces G2/M arrest <i>in vitro</i>, while reducing xenograft growth. Under metabolic stress (glucose deprivation/galactose adaptation), VPS37A triggers cell death via apoptosis, necroptosis, and ferroptosis. Mechanistically, VPS37A redirects TNFR1 to lysosomal degradation, suppressing NF-κB nuclear translocation and transcriptional activity.</p><p><strong>Conclusion: </strong>VPS37A deficiency drives CRC progression by sustaining TNFR1/NF-κB signaling under metabolic stress. Restoring VPS37A activity promotes TNFR1 degradation, offering a therapeutic strategy to counteract NF-κB-mediated treatment resistance in CRC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 8","pages":"2085-2105"},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CYMP-AS1 Promotes Ovarian Cancer Progression by Enhancing the Intracellular Translocation of hnRNPM and Reducing the Stability of AXIN2 mRNA.","authors":"Yuhan Wang, Yimei Meng, Wanqiu Xia, Yusen Liang, Yaru Wang, Peiling Li, Lei Fang","doi":"10.32604/or.2025.064367","DOIUrl":"10.32604/or.2025.064367","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer (OC) is a representative malignancy of the female reproductive system, with a poor prognosis. Long non-coding RNAs (lncRNAs) crucially affect tumor development. This study aimed to identify lncRNAs that potentially participated in OC.</p><p><strong>Methods: </strong>LncRNA expression in cells and tissues was quantified using reverse transcription-quantitative PCR, while fluorescence <i>in situ</i> hybridization determined their cellular localization. Various <i>in vitro</i> assays, together with a mouse xenograft model, were employed to elucidate the function of CYMP antisense RNA 1 (CYMP-AS1) in OC. The molecular mechanisms underlying CYMP-AS1 regulation were investigated through RNA pull-down and immunoprecipitation assays, immunofluorescence staining, western blotting, and mRNA stability assays.</p><p><strong>Results: </strong>This study identified a previously unreported lncRNA, CYMP-AS1, which exhibits increased expression in the cytoplasm of OC tissues and cells. Knockout of CYMP-AS1 reduced the OC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). CYMP-AS1 directly interacts with heterogeneous nuclear ribonucleoprotein M (hnRNPM), inducing its intracellular translocation and reducing the stability of Axis inhibition protein 2 (AXIN2) mRNA. This process ultimately elevated the expression of Wnt/β-catenin signaling pathway-related proteins.</p><p><strong>Conclusion: </strong>This study confirms CYMP-AS1 as a novel biomarker in OC progression and suggests that the CYMP-AS1/hnRNPM/AXIN2 axis may offer an innovative strategy for OC treatment.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 8","pages":"2141-2159"},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated PI3K/AKT signaling in oral squamous cell carcinoma: The tumor microenvironment and epigenetic modifiers as key drivers.","authors":"Vinothkumar Veerasamy, Veeravarmal Veeran, Siddavaram Nagini","doi":"10.32604/or.2025.064010","DOIUrl":"10.32604/or.2025.064010","url":null,"abstract":"<p><p>The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway is one of the most frequently dysregulated signaling networks in oral squamous cell carcinoma (OSCC). Although the tumor microenvironment (TME) and epigenetic modifiers are recognized to play a pivotal role in aberrant activation of the PI3K/AKT pathway in OSCC, the available evidence is fragmentary and a comprehensive analysis is warranted. This review evaluates the intricate mechanisms by which various components of the TME facilitate proliferation, apoptosis evasion, invasion, migration, angiogenesis, metastasis, as well as therapy resistance in OSCC through activation of PI3K/AKT signalling. The review has also analysed how epigenetic modifiers such as DNA methylation, histone modifications, and noncoding RNAs that have emerged as key players in orchestrating OSCC development and progression influence the PI3K/AKT pathway. Preclinical studies and clinical trials on the efficacy of PI3K/AKT inhibitors as viable options for OSCC treatment are discussed. Overall, this review supports the tenet that the PI3K/AKT pathway, which functions as a central hub through crosstalk with several oncogenic signaling pathways and overarching impact on all the hallmark traits of cancer, offers immense potential as a biomarker and oncotherapeutic target for OSCC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 8","pages":"1835-1860"},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPX4 predicts poor prognosis and regulates tumor proliferation and senescence in colorectal adenocarcinoma.","authors":"Y U Zhang, Qingkun Wang, Yue Han, Junjie Piao, Xiuying Jin","doi":"10.32604/or.2025.063395","DOIUrl":"10.32604/or.2025.063395","url":null,"abstract":"<p><strong>Background: </strong>Colorectal adenocarcinoma (COAD) is one of the most common gastrointestinal malignancies. There is a pressing need to recognize reliable biomarkers that can improve diagnostic accuracy, predict prognosis, and serve as effective molecular targets. Glutathione peroxidase 4 (GPX4) is an important antioxidant protein. Evidence demonstrates that abnormal expression of GPX4 is related to cancer initiation and progression. However, the role of GPX4 in COAD remains unclear.</p><p><strong>Methods: </strong>We employed bioinformatics analysis and conducted subsequent validation of biological processes, including cell counting kit-8 assay (CCK-8), colony formation assay, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), 5-ethynyl-2'-deoxyuridine assay (EdU), western blot, immunohistochemistry, senescence associated β-galactosidase (SA-β-gal) staining and immunofluorescence to explore the expression status, prognostic value and biological function of GPX4 in COAD.</p><p><strong>Results: </strong>Our data revealed that GPX4 mRNA expression was upregulated in COAD tissues and could predict the prognosis in patients with COAD. High GPX4 expression was associated with increased infiltration of malignant cells. We also performed a series of cell experiments confirming that GPX4 knockdown inhibited proliferation and induced cellular senescence, as determined by using CCK-8, colony formation, and EdU assay. In addition, SA-β-gal staining and senescence-associated secretory phenotype (SASP) components, such as P21 and Interleukin-6 (IL-6), were increased in GPX4 knockdown cells, while Lamin B1 was decreased. Moreover, we predicted that high expression of GPX4 was related to low immune cell infiltration.</p><p><strong>Conclusion: </strong>This study demonstrates that GPX4 is a potential prognostic biomarker and target gene for COAD.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 8","pages":"1933-1945"},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}