Journal of Cancer最新文献

{"title":"Resveratrol Induces Oxidative Stress and Downregulates GPX4 and xCT to Activate the Ferroptosis Pathway for Anti-Bladder Cancer Organoids.","authors":"Xiang Chen, Jun-Lin Lu, Hong Li, Guang-Yao Liu, Ting-Ting Li, Kang-Hua Xiao, Hai-Shan Ye, Sheng Li, Xu Chen, Jia Liu","doi":"10.7150/jca.109350","DOIUrl":"10.7150/jca.109350","url":null,"abstract":"<p><p><b>Purpose:</b> Resveratrol (RES) exhibits promising anti-bladder cancer (BC) effects. It causes cell death of BC cell lines and xenografts, but comprehensive analyses are required concerning oxidative status in RES-treated BC cells and its relevance with cell death patterns, and especially the efficacy of BC individuals. <b>Methods:</b> Two human BC cell lines (T24 and UM-UC-3) were cultured under 2D and 3D conditions to determine RES IC₅₀ values and 100 μM RES was thus used as a working concentration to treat 18 cases of BC-derived organoids (BCDOs). To observe the experimental results, this study will assess the oxidative stress status of bladder cancer cells, the corresponding potential cell death patterns, and the extent of inhibition by death inhibitors. <b>Results:</b> It revealed growth suppression of 10 RES-treated BCDOs (55.56%), accompanied by reduced mitochondrial potential and increased Reactive Oxygen Species (ROS) levels. Lipid peroxidation and downregulation of GPX4 and xCT, key antioxidant molecules of ferroptosis, were also found in RES-sensitive BC cells, and the inhibition rate of ferroptosis inhibitors increased to 22.57% of BCDOs. In addition, the supplementary experiment also indicated that it may be related to apoptosis and autophagy pathways. The above cellular and molecular alterations were not distinct in RES-insensitive BCDOs. <b>Conclusion:</b> RES possesses promising inhibitory effects on either BC cell lines or a large part (10/18) of BCDOs via enhancing oxidative stress and triggering the ferroptosis pathway or more. These findings underscore anti-BC properties of RES and its role as a potential personalized treatment option.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2613-2625"},"PeriodicalIF":3.3,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Traditional Chinese Medicine in combination with EGFR Inhibitors against Cancer.","authors":"Xiao Chen, Tiansheng Zheng, Bingjie Hao, Shumeng Lin, Liduo Yue, Lihong Fan","doi":"10.7150/jca.109420","DOIUrl":"10.7150/jca.109420","url":null,"abstract":"<p><p>Epidermal growth factor receptor (EGFR) is one of the most important and therapeutically significant targets in most cancer treatments, and EGFR-targeted therapy is widely performed to treat various tumors, such as non-small cell lung cancer. Although EGFR-targeted therapy has fewer side effects than conventional chemotherapy, they have limited applications and are prone to drug resistance. Traditional Chinese medicine (TCM), are promising solutions to address these challenges because of their biological activities, such as inhibition of EGFR-related signaling pathways, reversal of drug resistance, and mitigation of side effects of targeted therapy. Moreover, TCM is characterized by multiple targets, few side effects and good therapeutic effect Here, we summarized several typical traditional Chinese medicine monomers derived from traditional Chinese medicine that can be used along with EGFR inhibitors, as well as herbal plants with potential for natural product development and TCM. We focused on their mechanisms of action underlying the reversal of drug resistance, enhancement of drug efficacy, and mitigation of side effects; we also assessed relevant clinical studies that are available. However, the potential adverse effects (e.g., drug-drug interactions, hepatotoxicity, and immune-related side effects) of TCMs along with EGFR inhibitors need to be further investigated. This article provided new perspectives on the use of TCMs in EGFR-targeted therapy and emphasized the importance of safety assessment in future studies.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2595-2612"},"PeriodicalIF":3.3,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Quercetin as a Natural MMP1 Inhibitor for Overcoming Cisplatin Resistance in Epithelial Ovarian Cancer.","authors":"Shubo Wang, Ziming Zhao, Lili Yu, Jue Wang, Yue Ouyang, Hua Zhou, Weixing Shen, Qibiao Wu","doi":"10.7150/jca.110517","DOIUrl":"10.7150/jca.110517","url":null,"abstract":"<p><p><b>Background:</b> It is challenging to find a therapeutic Chinese medicine monomer (CHMs) for platinum-resistant patients, who currently have few treatment options, due to the complex mechanisms and the large number of CHMs available. This study aimed to identify CHM to overcome cisplatin resistance in EOC through bioinformatics analysis with <i>in vitro</i> experiment. <b>Methods:</b> This study used a strategy opposite to conventional network pharmacology. RNA expression of cisplatin sensitive and resistant EOC cell lines was obtained from the GEO database. Through differential expression gene (DEG) analysis, PPI network analysis, and survival analysis, we identified hub genes related to platinum resistance. CHMs targeting these hub genes were identified from the HIT 2.0 and molecular docking, molecular dynamics (MD) simulations, and SPR assay were used to validate their binding ability. Then, the anti-cancer effects of CHM in cisplatin-resistant cell lines were verified via <i>in vitro</i> experiment. <b>Results:</b> 16 hub genes were selected through DEG and PPI network analysis. Following validation via survival analysis in the TCGA-OV cohort, the investigation ultimately focused on MMP1. Western blotting results demonstrated that MAPK signaling pathway activation induced MMP1 expression in cisplatin-resistant EOC cells. 22 CHMs targeting MMP1 were found in HIT 2.0 and quercetin was demonstrated the strong affinity of quercetin for MMP1 via molecular docking, MD simulations and SPR assay. Quercetin also exhibited strong binding affinity to other hub genes, including EGR1, STAT1, and PRKCA. <i>In vitro</i> experiments demonstrated that quercetin effectively inhibited the proliferation, apoptosis resistance, invasion, and migration of cisplatin-resistant EOC cells. The combination of cisplatin and quercetin had a strong synergistic effect, as indicated by the ZIP synergy score (≥10). <b>Conclusion:</b> Our study identified quercetin, which functions by targeting multiple cisplatin resistance-related proteins, including MMP1, as a potential therapeutic CHM for cisplatin resistant EOC. This study also explored quercetin's mechanisms against platinum-resistant ovarian cancer. By identifying hub platinum-resistance associated genes and screening potential CHMs through bioinformatics, computer simulation, and <i>in vitro</i> experiments, this integrated analytical approach also offers a reference for discovering CHMs for other diseases.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2578-2594"},"PeriodicalIF":3.3,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ursolic Acid induces ferroptosis by affecting redox balance and FADS2-mediated unsaturated fatty acid synthesis in Non-Small Cell Lung Cancer.","authors":"Lanlan Yang, Yuan Fang, Yuli Wang, Yingbin Luo, Yanbin Pan, Jianchun Wu, Yan Li","doi":"10.7150/jca.105863","DOIUrl":"10.7150/jca.105863","url":null,"abstract":"<p><p>Ursolic Acid (UA) is a naturally occurring pentacyclic triterpenoid compound that is prevalent in various medicinal plants and fruits. It has garnered significant attention due to its broad spectrum of anticancer properties. In this study, we evaluated the antitumor effects of UA on Non-Small Cell Lung Cancer (NSCLC).UA significantly inhibited NSCLC viability and induced cell death in a time- and dose-dependent manner. Furthermore, the administration of UA resulted in an elevation of intracellular reactive oxygen species (ROS), lipid ROS, and ferrous iron levels, while concurrently suppressing the expression of SLC7A11, glutathione, and GPX4. Consequently, this led to an augmentation in the concentration of the lipid peroxidation substrate, malondialdehyde. All the changes were effectively attenuated by the ferroptosis inhibitor Ferrostatin-1(Fer-1) and Deferoxamine (DFO). Moreover, similar observations were made in animal experiments. The sequencing data indicate that UA influences ferroptosis by modulating Fatty Acid Desaturase-2 (FADS2). The reintroduction of FADS2 through ectopic expression restored the resistance to ferroptosis induced by UA in A549 cells, while the addition of exogenous oleic acid (OA) counteracted the impact of UA on the oxidative response. These results suggest that UA induces ferroptosis in NSCLC by affecting redox pathways and the FADS2-mediated synthesis of unsaturated fatty acids.These studies collectively underscore the promising role of UA in the development of effective anticancer therapies.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2553-2566"},"PeriodicalIF":3.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theaflavin-3,3'-digallate triggers apoptosis in osteosarcoma cells via the caspase pathway.","authors":"Yat-Yin Law, Yi-Hsien Hsieh, Yih-Shou Hsieh, Yi-Hsun Lee, Chia-Ling Tang, Chia-Yi Lee, Shun-Fa Yang, Shu-Chen Chu, Pei-Ni Chen","doi":"10.7150/jca.111718","DOIUrl":"10.7150/jca.111718","url":null,"abstract":"<p><p>Osteosarcoma is a cancer associated with a guarded prognosis. Various compounds can induce apoptosis in osteosarcoma cells. Theaflavin-3,3'-digallate (TF3) has been demonstrated to alter cell growth and induce apoptosis in various cancer cells. The present study investigated the apoptotic effect of TF3 on osteosarcoma cells. It further explored key apoptotic pathways activated by TF3. Viability of 143B and U2OS osteosarcoma cells after TF3 treatment was assessed. The effects of TF3 on key apoptotic pathways were analyzed. Furthermore, a xenograft mouse model of osteosarcoma was established for <i>in vivo</i> experiments. The results indicated that TF3 significantly reduced the viability of 143B and U2OS cells. Western blotting revealed that TF3 upregulated the expression of cleaved caspase-3 and cleaved caspase-9 in osteosarcoma cells. In addition, TF3 increased the levels of phosphorylated histone H2Ax, Bax, Bak1, and cytochrome c, while reducing the levels of Mcl-1 and survivin in osteosarcoma cells. Furthermore, TF3 significantly reduced the average tumor volume in the xenograft model. Overall, this study suggests that TF3 induces apoptosis in osteosarcoma cells, primarily by regulating the caspase pathway.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2567-2577"},"PeriodicalIF":3.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development And Validation of An RNA Binding Protein-Associated Prognostic Model for Colon Adenocarcinoma.","authors":"Xiajing Yu, Daixin Guo, Jie Gao, Jialing Hu, Wenyige Zhang, Qijun Yang, Jingyi Wang, Yingcheng He, Kaili Liao, Xiaozhong Wang","doi":"10.7150/jca.103477","DOIUrl":"10.7150/jca.103477","url":null,"abstract":"<p><p><b>Purpose:</b> We aimed to identify prognostic RNA-binding proteins (RBP) in colon cancer, analyze their biological functions, and develop predictive models for patient prognosis. <b>Materials and Methods:</b> We downloaded COAD's RNA sequencing data from the Cancer Genome Atlas (TCGA) database, and the expression and prognostic value of these RBPs in COAD were systematically evaluated. Differential expression, KEGG, and GO enrichment analyses were then performed. Cytoscape was used to visualize the protein-protein interaction network, and Cox regression was used to establish a predictive model. Finally, the expression of RBP was verified by the HPA database and immunohistochemical staining. <b>Results:</b> A total of 472 differentially expressed RBPs were detected, including 321 up-regulated RBPs and 151 down-regulated RBPs. Four RBPs (MSI2, EZH2, NCL, TERT) were identified as key prognostic genes and used to construct prognostic models, based on this model, the overall survival (OS) of patients in high-risk subgroup was worse than that of patients in the low-risk subgroup. The area under the curve of time-dependent receiver operator characteristic curve of TCGA training set and Gene Expression Omnibus (GEO) validation set was 0.607 and 0.638 respectively, which confirmed that the prognosis model was good, it showed a good ability to identify COAD. <b>Conclusion:</b> In general, our prognostic model is based on 4 RBPs encoding genes, which greatly reduces the cost of sequencing and is more conducive to clinical applications.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2537-2552"},"PeriodicalIF":3.3,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyroptosis-Related Gene Signatures Enable Robustly Diagnosis, Prognosis and Immune Responses Prediction in Uterine Corpus Endometrial Carcinoma.","authors":"Xuanming Chen, Xiangyu Jin, Jiafu Wang, Hanfei Li, Chuanfang Wu, Jinku Bao","doi":"10.7150/jca.104826","DOIUrl":"10.7150/jca.104826","url":null,"abstract":"<p><p><b>Purpose:</b> Uterine corpus endometrial carcinoma (UCEC) is a gynecological malignancy with poor prognosis and high lethality rates. Pyroptosis, a pro-inflammatory programmed cell death pattern, significantly influences tumor growth, development, and metastasis. We intend to explore whether pyroptosis-related genes can be screened as targets for early detection and patient prognosis. <b>Methods:</b> We used nine common machine learning algorithms to build classifiers based on the pyroptosis-related genes, evaluated the classifiers' performance using metrics like the receiver operating characteristic curve (ROC), and verified the results using external datasets. Using Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, we built a predictive model. ROC and univariate/multivariate Cox analyses were used to assess the model's performance and its independence in predicting patient prognosis. We used a variety of statistical methods and algorithms to investigate the connection between tumor immunity and pyroptosis-related genes. <b>Results:</b> We identified 26 pyroptosis-related genes associated with the diagnosis and prognosis of UCEC. We found the logistic regression classifier performing the best. We then constructed a predictive model based on seven PRGs about <i>IRF2, TIRAP, BAK1, GSDMD, CHMP2A, GPX4, CHMP2B</i>. The pyroptosis-related gene risk signature (PRGRS) effectively classified UCEC patients. We demonstrated that PRGRS independently impacted UCEC prognosis and confirmed its expression using qRT-PCR experiments. Furthermore, we found associations between PRGRS and tumor immune response. <b>Conclusion:</b> Our study highlights novel pyroptosis-related gene signatures that may be utilized for early screening and prognosis prediction in UCEC patients, offering potential targets for future research and guidance for personalized anticancer therapies.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2516-2536"},"PeriodicalIF":3.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia regulates glycolysis through the HIF-1α/BMAL1/ALDOC axis to reduce oxaliplatin sensitivity in colorectal cancer.","authors":"Jialing Ran, Feifei Li, Lei Zhan, Yue Jin, Qian Dong, Xiaoyan Li, XiaoXi Li, Qian Fei, Jingdong Zhang","doi":"10.7150/jca.108582","DOIUrl":"10.7150/jca.108582","url":null,"abstract":"<p><p><b>Background:</b> Oxaliplatin (L-OHP) is a first-line chemotherapy agent for advanced colorectal cancer (CRC), but the development of resistance often compromises its efficacy. Tumor hypoxia and metabolic reprogramming are known to influence chemotherapy sensitivity, yet their interrelationship remains inadequately explored. <b>Methods:</b> <i>In vitro</i> assays were conducted using human colorectal cancer cell lines (DLD1 and LoVo) under hypoxic conditions induced by cobalt chloride (CoCl2). The expression levels of key proteins involved in the HIF-1α/BMAL1/ALDOC pathway were assessed through Western blotting and quantitative real-time PCR (qPCR). Cell viability, apoptosis, and glycolytic activity were evaluated using CCK-8 assays, flow cytometry, and lactate/ATP measurements. <b>Results:</b> Hypoxia significantly enhanced glycolysis in CRC cells, decreasing sensitivity to L-OHP. The HIF-1α/BMAL1/ALDOC axis was identified as a crucial mediator in this process, with HIF-1α upregulating BMAL1, which increased ALDOC expression. This cascade promoted glycolytic activity and reduced apoptosis in hypoxic conditions. Notably, a positive correlation between HIF-1α and ALDOC expression was confirmed in clinical CRC samples. <b>Conclusion:</b> The findings reveal a novel mechanism by which hypoxia diminishes L-OHP sensitivity in CRC through the HIF-1α/BMAL1/ALDOC pathway. These insights provide potential biomarkers for predicting treatment outcomes and suggest new therapeutic strategies to enhance chemosensitivity in colorectal cancer.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2503-2515"},"PeriodicalIF":3.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In vitro</i> antioxidant, anticholinesterase, and antiproliferative activities of methanol extracts of <i>Crateva religiosa</i> bark.","authors":"Md Sifat Hossain, Md Abdul Majed Patwary, Sharmin Akther Rupa, Mohsin Kazi, Ashok Kumar, Khalid M Alghamdi, Mohammed Mahbubul Matin, Md Rezaur Rahman","doi":"10.7150/jca.94492","DOIUrl":"10.7150/jca.94492","url":null,"abstract":"<p><p><b>Background:</b> <i>C. religiosa</i> has traditionally been applied to treat heart disease, chronic weight loss, improved digestion, memory loss, convulsion and epilepsy, psychological problems, and neurologic pains. <b>Purpose:</b> Prior studies have already elucidated the potential therapeutic effects of C. religiosa. However, in this work, the bark extract of <i>C. religiosa</i> was studied systematically to investigate its antioxidant, anticholinesterase, and antiproliferative activities, focusing on potential applications in treating Alzheimer's disease (AD) and cancer. <b>Study Design and Methods:</b> The dried coarse powder of <i>C. religiosa</i> bark was cold-extracted in methanol and evaporated to dryness. It was then successively fractionated into petroleum ether (PEF), dichloromethane (DMF), and ethyl acetate (EEF) fractions. The Folin-Ciocalteu reagent and AlCl₃ approaches were utilized to evaluate the total phenol and flavonoid contents, respectively, and the DPPH (2,2-diphenyl-1-picrylhydrazyl) and phosphomolybdenum assays were employed to determine the antioxidant activity of each fraction. The DMF was tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) by employing the Ellman method, while all fractions were tested for antiproliferative activity against HepG2 and A549 cell lines by MTT assay. <b>Results:</b> The DMF displayed the highest phenolic content (124.8 ± 17.5 mg gallic acid equivalent/g of dry extract) and flavonoid content (211.1 ± 4.8 mg quercetin equivalent/g of dry extract). In the phosphomolybdenum assay, its antioxidant IC50 value was 25 ± 1 µg/mL. Additionally, the DMF fraction exhibited significant inhibition activity against AChE and BChE, with IC50 values of 455 ± 1 and 450 ± 1 μg/mL, respectively. In terms of anti-proliferative activity, the DMF exhibited an IC50 value of 29.2 µM against the HepG2 cell line, while the EAF showed IC50 values of 24.7 µM in the A549 cell line. <b>Conclusion:</b> The potent activity of <i>C. religiosa</i> as an antioxidant, along with its significant inhibition of AChE and BChE, positions it as a promising candidate for Alzheimer's disease treatment. Furthermore, its robust inhibition of human liver and lung cancer cells suggests its potential as a therapeutic agent against cancer.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2492-2502"},"PeriodicalIF":3.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinoic acid metabolism related gene CYP26B1 promotes tumor stemness and tumor microenvironment remodeling in bladder cancer.","authors":"Jun Gu, Zhen-Duo Shi, Kun Pang, Lin Hao, Wei Wang, Cong-Hui Han","doi":"10.7150/jca.101406","DOIUrl":"10.7150/jca.101406","url":null,"abstract":"<p><p><b>Background</b>: The previous studies have shown that the retinoic acid (RA) metabolism is closely related to the cancer stemness, but its role in bladder cancer development has not been fully investigated. <b>Methods</b>: We conducted a comprehensive analysis of mutations, copy number variations and transcriptional changes of RA metabolism related genes in bladder cancer cells. We evaluated the activity of RA metabolism in tumor cells by using single cell transcriptome data and identified differentially expressed genes (DEGs) in cell subsets with high RA-metabolism score. We also investigated and verified the biological function of <i>CYP26B1</i> (one of RA metabolism related genes) <i>in vitro</i>. Additionally, we analyzed and verified the relationship between <i>CYP26B1</i> and tumor immune microenvironment by multiplex immunohistochemical (mIHC). <b>Results</b>: Comprehensive analysis indicates that the mutation rate of RA metabolism related genes in bladder cancer is about 20%, with significant gene amplification observed in <i>RDH10</i> and <i>CYP26B1.</i> We identified a group of subsets with significantly increased RA metabolism activity in bladder cancer tumor epithelial cells and found that this subgroup was significantly associated with poor prognosis (p < 0.05). <i>CYP26B1</i> was identified as a potential therapeutic target. It was found that <i>CYP26B1</i> is significantly correlated with tumor stemness and differentiation. <i>In vitro</i> experiments confirmed that overexpression of <i>CYP26B1</i> can significantly enhance the proliferation and migration of tumor cells. <b>Conclusion:</b> These results suggest that CYP26B1 may be closely related to the remodeling of the tumor microenvironment and may become a potential therapeutic target for bladder cancer.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2476-2491"},"PeriodicalIF":3.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}