Cancer Genomics & Proteomics最新文献

{"title":"SCAMP3 and EPS8 Cooperatively Regulate EGFR Signaling to Promote Enzalutamide Resistance and Metastatic Potential in Prostate Cancer.","authors":"Wei-Lun Huang, Pei-Fang Hsieh, Sih-Han Chen, Richard Chen-Yu Wu, Hsing-Cha Mai, Chun-Hsien Wu, See-Tong Pang, Yu-Lin Yang, Victor Chia-Hsiang Lin","doi":"10.21873/cgp.20549","DOIUrl":"10.21873/cgp.20549","url":null,"abstract":"<p><strong>Background/aim: </strong>Prostate cancer is the second most common malignancy among men worldwide, with progression to castration-resistant prostate cancer (CRPC) posing significant therapeutic challenges. Enzalutamide, a second-generation androgen receptor antagonist, initially demonstrates efficacy in treating metastatic CRPC; however, resistance inevitably develops. Dysregulation of the epidermal growth factor receptor (EGFR) signaling pathway has been implicated in therapy resistance and metastatic progression. Secretory carrier membrane protein 3 (SCAMP3) and epidermal growth factor receptor substrate 8 (EPS8) are known regulators of EGFR trafficking and signaling. This study aimed to investigate their cooperative roles in enzalutamide-resistant prostate cancer cells.</p><p><strong>Materials and methods: </strong>LNCap prostate cancer cells and their enzalutamide-resistant derivatives (LNCap-Enz) were treated with 100 ng/ml epidermal growth factor (EGF). Protein expression and interactions were analyzed by Western blotting and co-immunoprecipitation. SCAMP3 and EPS8 were knocked down using shRNA technology, while complementary overexpression studies were conducted using pcDNA-SCAMP3 and pcDNA-EPS8 vectors. Effects on EGF receptor (EGFR) expression and downstream signaling molecules (STAT3, AKT, ERK) were evaluated in both loss-of-function and gain-of-function models.</p><p><strong>Results: </strong>EGF stimulation enhanced the expression of EGFR, SCAMP3, and EPS8 in both LNCap and LNCap-Enz cells while promoting formation of a protein complex involving these proteins and the androgen receptor (AR-V7). Knockdown of SCAMP3 or EPS8 reduced EGFR expression and attenuated STAT3, AKT, and ERK activation. Conversely, overexpression of SCAMP3 or EPS8 increased EGFR levels and enhanced downstream signaling activation. These bidirectional effects highlight the functional interdependence between SCAMP3 and EPS8 in regulating EGFR stability and signaling.</p><p><strong>Conclusion: </strong>SCAMP3 and EPS8 cooperatively maintain EGFR stability and signaling in prostate cancer cells, playing a critical role in enzalutamide resistance and metastatic progression. Targeting the SCAMP3-EPS8-EGFR axis offers promising therapeutic opportunities for advanced prostate cancer.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 6","pages":"953-970"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12577594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145387256","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":"Differential Proteomic Analysis of DEN-induced Hepatocellular Carcinoma in Male and Female Balb/c Mice Reveals Novel Sex-Specific Markers.","authors":"Salmma Salamah Salihah, Muhammad Tahir, Bareera Bibi, Rabia Sultan, Martin R Larsen, Munazza Raza Mirza, Sana Mahmood, Muhammad Rizwan Alam, Jamila Iqbal, William C Cho, Asma Gul","doi":"10.21873/cgp.20540","DOIUrl":"10.21873/cgp.20540","url":null,"abstract":"<p><strong>Background/aim: </strong>Hepatocellular carcinoma (HCC) is one of the leading causes of hepatic malignancy with a higher prevalence in males compared to females; however, the distinct underlying mechanisms contributing to this disparity remain poorly understood.</p><p><strong>Materials and methods: </strong>In this study, we aimed to investigate comparative proteome profiling of a diethylnitrosamine (DEN) induced HCC model in male and female Balb/c mice. We extracted proteins from the liver tissue of DEN-treated male and female mice and their corresponding controls and subjected them to mass spectrometry and subsequent bioinformatics analyses.</p><p><strong>Results: </strong>We identified 170 and 146 differentially expressed proteins (DEPs) in female and male mice, respectively. We identified chemical carcinogenesis, oxidative phosphorylation, actin binding and mitochondrial respiration as the shared pathways between the two groups. In addition, we identified distinct signaling pathways in DEN-treated male and female mice. Female mice showed enrichment in fatty acid biosynthesis, metabolism, degradation, and cytochrome P450 clusters. In contrast, in male mice, pathways were enriched in tryptophan metabolism, apoptotic execution phase and glutathione metabolism. Further, we identified the top ten genes ranked by highest maximal clique centrality, by protein-protein interaction analysis of differentially expressed proteins (DEPs) in both sexes. Of these hub genes, female mice showed up-regulation of previously unimplicated, NDUFA8 and ATP5H proteins which were associated with poor patient survival. On the other hand, in DEN-treated male mice up-regulation of RPS3 was associated with poor survival.</p><p><strong>Conclusion: </strong>In conclusion, our research provides sex-specific proteomic signatures in DEN-induced HCC. The identification of proteins associated with ribosomal subunits in males, and two previously unimplicated mitochondrial complex I proteins in females as prognostic markers suggests novel therapeutic targets that may inform sex-tailored treatment strategies for HCC.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 6","pages":"912-928"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12577593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145387225","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":"Strong Association Between Higher Expression of Anillin Actin-binding Protein in Pancreatic Adenocarcinoma Tissues and Patient Survival Analyzed With the UALCAN and GEPIA Platforms Using the TCGA Database.","authors":"Shin-Nosuke Yamashita, Yoshiatsu Tanaka, Shajedul Islam, Takao Kitagawa, Kazuhiro Tokuda, Durga Paudel, Sarita Giri, Tohru Ohta, Fumiya Harada, Hiroki Nagayasu, Yasuhiro Kuramitsu","doi":"10.21873/cgp.20555","DOIUrl":"10.21873/cgp.20555","url":null,"abstract":"<p><strong>Background/aim: </strong>Pancreatic adenocarcinoma (PAAD) is one of the most lethal cancers worldwide, with more than 95% of PAAD patients not surviving beyond 5 years. Due to its rapid progression, in most cases there is no time for treatment by the time the disease is diagnosed, and metastases have developed in many organs. Therefore, there is currently a need to discover prognostic markers. Anillin actin-binding protein (ANLN) is an actin-binding protein involved in cell division. Its increased expression has been reported in many types of cancer, suggesting that it may be strongly involved in the progression of cancer malignancy, such as invasion and metastasis. The purpose of this study was to use bioinformatics to examine the possibility that ANLN may be a useful prognostic marker for PAAD.</p><p><strong>Materials and methods: </strong>The Gene Expression Profiling Interactive Analysis (GEPIA) and the University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) bioinformatics platforms were used to analyze <i>ANLN</i> mRNA expression, protein revel, and survival in patients with PAAD from The Cancer Genome Atlas (TCGA) database.</p><p><strong>Results: </strong><i>ANLN</i> mRNA and protein levels were found to be significantly higher in PAAD tissues compared to normal pancreatic tissues, and this elevation correlated with poor prognosis in PAAD patients.</p><p><strong>Conclusion: </strong>Increased expression of <i>ANLN</i> mRNA and protein was detected in PAAD tissues compared to normal pancreatic tissues by the GEPIA and UALCAN platforms of the TCGA database. Increased <i>ANLN</i> expression correlated with poor patient prognosis. These results suggest that <i>ANLN</i> may be a promising prognostic biomarker in PAAD.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 6","pages":"1061-1068"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12577607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145387323","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":"C1orf50 Accelerates Epithelial-Mesenchymal Transition and the Cell Cycle of Hepatocellular Carcinoma.","authors":"Atsushi Tanaka, Yusuke Otani, Masaki Maekawa, Anna Rogachevskaya, Tirso Peña, Vanessa D Chin, Shinichi Toyooka, Michael H Roehrl, Atsushi Fujimura","doi":"10.21873/cgp.20541","DOIUrl":"10.21873/cgp.20541","url":null,"abstract":"<p><strong>Background/aim: </strong>Hepatocellular carcinoma (HCC) is a heterogeneous liver cancer with limited treatment options and a poor prognosis in advanced stages. To identify novel biomarkers and therapeutic targets, we investigated the role of chromosome 1 open reading frame 50 (<i>C1orf50</i>), a gene with a previously uncharacterized function in HCC.</p><p><strong>Materials and methods: </strong>We performed a comprehensive transcriptome data analysis of the human hepatocellular carcinoma project from The Cancer Genome Atlas (TCGA) and subsequently validated the oncogenic roles of C1orf50 using HCC cell lines.</p><p><strong>Results: </strong>Using transcriptomic and clinical data from TCGA, we stratified 355 primary HCC samples based on C1orf50 expression levels. Patients with high C1orf50 expression exhibited significantly shorter overall survival, suggesting its association with aggressive tumor behavior. Differential expression and enrichment analyses revealed that C1orf50-high tumors were enriched in oncogenic pathways, including epithelial-mesenchymal transition (EMT), cell cycle activation, and stemness-related properties. Transcriptional regulatory network analysis detected 456 significantly dysregulated regulons, including ZEB1/2 and E2F2, key drivers of EMT and cell cycle, in the C1orf50-high group. In addition, we observed increased YAP1/TAZ signaling, further linking C1orf50 to stemness and therapeutic resistance. Functional data from CRISPR-based dependency screening suggested that several transcription factors up-regulated in the C1orf50-high state, such as ZBTB11 and CTCE, are essential for the survival of HCC cells. These findings indicate potential therapeutic vulnerabilities and support the rationale for targeting C1orf50-associated pathways.</p><p><strong>Conclusion: </strong>C1orf50 is a novel biomarker of poor prognosis in HCC and a key regulator of oncogenic features such as EMT, cell cycle progression, and stemness. This study highlights the therapeutic potential of targeting C1orf50-related networks in aggressive subtypes of liver cancer.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 6","pages":"836-849"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12577603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145387160","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":"Angiogenic Edge of ANGPT2: Genetic Variants Shape Prostate Cancer Prognosis on Androgen Deprivation Therapy.","authors":"Yei-Tsung Chen, Pin-Yi Chen, Chi-Fen Chang, Chao-Yuan Huang, Chia-Cheng Yu, Victor C Lin, Hao-Han Chang, Te-Ling Lu, Shu-Pin Huang, Bo-Ying Bao","doi":"10.21873/cgp.20551","DOIUrl":"10.21873/cgp.20551","url":null,"abstract":"<p><strong>Background/aim: </strong>Prostate cancer, a leading global malignancy, exhibits variable progression influenced by angiogenesis, the formation of new blood vessels critical for tumor growth and metastasis. We investigated the impact of genetic variants of angiogenesis-related genes on the survival outcomes of patients with prostate cancer receiving androgen deprivation therapy (ADT).</p><p><strong>Materials and methods: </strong>We conducted a genetic association study of 87 single-nucleotide polymorphisms across seven angiogenic genes in 630 patients with prostate cancer undergoing ADT. Survival analysis was used to assess progression-free survival (PFS) and overall survival (OS). Functional analyses, including gene ontology and pathway enrichment, were performed to elucidate the underlying biological mechanisms.</p><p><strong>Results: </strong><i>ANGPT2</i> rs2959822 was significantly associated with PFS [hazard ratio (HR)=1.22, <i>p</i>=0.015] and OS (HR=1.22, <i>p</i>=0.021). The minor allele A increased the risk of disease progression and mortality. Functional analyses revealed that rs2959822 influenced <i>ANGPT2</i> expression. Elevated <i>ANGPT2</i> expression was correlated with higher Gleason score, advanced tumor stage, and shorter PFS. Gene set enrichment analysis linked <i>ANGPT2</i> to epithelial-mesenchymal transition (EMT), demonstrating positive correlations with several key EMT genes, along with increased immune cell infiltration, indicating its multifaceted oncogenic roles.</p><p><strong>Conclusion: </strong><i>ANGPT2</i> rs2959822 influences the survival outcomes of patients with prostate cancer undergoing ADT. In addition to angiogenesis, <i>ANGPT2</i> plays a critical role in prostate cancer progression by promoting EMT and modulating the tumor immune microenvironment.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 6","pages":"991-1005"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12577598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145387249","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":"Verbascoside Suppresses Epithelial-Mesenchymal Transition and Mitochondrial Biogenesis by Targeting Anti-senescence Signaling in Castration-resistant Prostate Cancer.","authors":"Hsing-Chia Mai, Pei-Fang Hsieh, Chun-Hsien Wu, Richard C Wu, Sih-Han Chen, Wei-Lun Huang, Mu-Chiao Tung, Yu-Lin Yang, Victor C Lin, Chiang-Ting Wang","doi":"10.21873/cgp.20554","DOIUrl":"10.21873/cgp.20554","url":null,"abstract":"<p><strong>Background/aim: </strong>Verbascoside, a natural phenylethanoid glycoside, has demonstrated significant therapeutic potential in castration-resistant prostate cancer (CRPC). This study aimed to elucidate the mechanistic pathways through which verbascoside exerts its antisenescence and anti-metastatic effects, focusing on epithelial-mesenchymal transition (EMT), oxidative stress response, and mitochondrial biogenesis regulation in CRPC cells.</p><p><strong>Materials and methods: </strong>CRPC cell models were treated under various concentrations of verbascoside. EMT markers, oxidative stress-related proteins, mitochondrial biogenesis regulators, and proinflammatory cytokines were assessed using Western blotting and ELISA. Cellular senescence and proliferation were evaluated through analysis of p38 MAPK activation and key cell cycle regulators (p16, p21, p27, and retinoblastoma protein (Rb).</p><p><strong>Results: </strong>Verbascoside treatment inhibited EMT, reduced oxidative stress markers, and enhanced mitochondrial biogenesis, supporting cellular energy homeostasis. It also suppressed the secretion of proinflammatory cytokines, including interleukin (IL)-6, IL-8, and IL-1, associated with the senescence-associated secretory phenotype. Downstream signaling analysis revealed that verbascoside decreased p38 MAPK activation and down-regulated p16, p21, p27, and Rb, thereby attenuating prosenescence signaling and proliferation control.</p><p><strong>Conclusion: </strong>Verbascoside attenuates CRPC progression by modulating EMT, alleviating oxidative damage, enhancing mitochondrial function, and inhibiting prosenescence signaling pathways. These findings highlight its therapeutic potential for targeting senescence-related mechanisms in aggressive prostate cancer and provide a basis for future CRPC management strategies.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 6","pages":"1044-1060"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12577602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145387283","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":"Lipid Metabolic Reprogramming During Progression to Castration-resistant Prostate Cancer Identified by Quantitative Proteomics.","authors":"Hyunchae Sim, Subin Bae, Chai Won Park, So Young Choi, Kwang-Hyeon Liu, Eun Hye Lee, Bum Soo Kim, Jae-Wook Chung, Yun-Sok Ha, Jun Nyung Lee, Wonhwa Lee, Tae Gyun Kwon, Sangkyu Lee","doi":"10.21873/cgp.20548","DOIUrl":"10.21873/cgp.20548","url":null,"abstract":"<p><strong>Background/aim: </strong>The progression of hormone-sensitive prostate cancer (HSPC) to castration-resistant prostate cancer (CRPC) as a result of resistance to androgen deprivation therapy (ADT) remains a major challenge in prostate cancer treatment.</p><p><strong>Materials and methods: </strong>To explore the underlying mechanisms, we performed deep comparative proteomic profiling of HSPC and CRPC cell lines. LNCaP and C4-2 cell lines were cultured in isotopically labeled medium, combined, and digested, followed by liquid chromatography-mass spectrometry (LC-MS/MS) and bioinformatic analyses.</p><p><strong>Results: </strong>Using SILAC-based proteomic analysis, 3,578 proteins were identified, with 2,474 quantified. In C4-2 cells, 41 proteins were significantly up-regulated, while 201 were down-regulated (fold-change >1.5 or <1.5-1, <i>p</i><0.05). KEGG pathway analysis linked the increased proteins to fatty acid metabolism and biosynthesis of unsaturated fatty acids. Lipidomic analysis showed a significant rise in fatty acids like DHA, palmitic acid, stearic acid, and arachidic acid, aligning with the proteomic findings.</p><p><strong>Conclusion: </strong>These results suggest that fatty acids play a key role in HSPC's progression to CRPC, possibly indicating that CRPC cells themselves may generate fatty acids.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 6","pages":"940-952"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12577596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145387322","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":"PPIL1 Drives Hepatocellular Carcinoma Progression and Cancer Stem Cell Self-renewal Through DAAM2-mediated Wnt/β-Catenin Activation.","authors":"Jiayi Wu, Shiyuan Chang, Shuo Chen, Y U Qi, Weijun Su","doi":"10.21873/cgp.20535","DOIUrl":"10.21873/cgp.20535","url":null,"abstract":"<p><strong>Background/aim: </strong>Hepatocellular carcinoma (HCC) accounts for ~90% of primary liver cancer, which ranks as the third-leading cause of global cancer mortality. Emerging evidence establishes cancer stem cells (CSCs) as central regulators of HCC progression, metastasis, and therapeutic resistance, with stemness-related pathways like Wnt/β-catenin signaling critically maintaining CSC self-renewal. In this study, we aimed to investigate the role of Peptidyl-prolyl isomerase-like 1 (PPIL1) in HCC progression and CSC self-renewal.</p><p><strong>Materials and methods: </strong>PPIL1 expression patterns were systematically analyzed using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) data and validated in primary HCC specimens <i>via</i> qRT-PCR and western blot. PPIL1 was knocked down in HCC cell lines using shRNAs, and cell viability, migration, and sphere formation were assessed <i>in vitro</i>. Xenograft mouse models were established to evaluate the effects of PPIL1 on tumor growth kinetics and liver CSC-related properties. Transcriptome analysis was performed to identify downstream targets and signaling pathways affected by PPIL1 knockdown.</p><p><strong>Results: </strong>Our analysis revealed significantly elevated PPIL1 expression in HCC tumors and liver CSCs, with its expression level positively correlating with tumor stage and histological grade. PPIL1 knockdown effectively suppressed HCC cell proliferation, migration, and <i>in vivo</i> tumor growth. The essential role of PPIL1 in liver CSC maintenance was demonstrated by impaired sphere-forming capacity and diminished tumor initiation potential. Mechanistic studies identified PPIL1 as a regulator of Wnt/β-catenin signaling through transcriptional up-regulation of dishevelled associated activator of morphogenesis 2 (DAAM2).</p><p><strong>Conclusion: </strong>Our findings suggest PPIL1 to be a crucial regulator of HCC progression and liver CSC maintenance <i>via</i> DAAM2-mediated Wnt/β-catenin activation. This positions PPIL1 as a promising molecular target for HCC therapy, with particular relevance for addressing CSC-driven therapeutic resistance.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 5","pages":"760-774"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12402719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944112","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":"Bladder Cancer: Role of Circular RNAs in Oncogenesis, Tumor Suppression, and Therapeutic Target Identification.","authors":"Satu Nahkuri, Ulrich H Weidle","doi":"10.21873/cgp.20528","DOIUrl":"10.21873/cgp.20528","url":null,"abstract":"<p><p>In order to identify new treatment modalities and targets for the treatment of bladder cancer (BLC), we have searched the literature (PubMed) for circular RNAs (circRNAs) that mediate efficacy in preclinical BLC-related <i>in vivo</i> systems. Pathogenesis-affecting circRNAs can be up-regulated or down-regulated depending on their function as oncogenes or tumor suppressors. We have grouped the identified circRNAs according to functional aspects or protein categories, such as involvement in drug resistance, transmembrane proteins, secreted proteins, mediators of signaling, enzymes with pathogenic potential, transcription factors, as well as circRNAs involved in microRNA (miR) processing and epigenetic modifications. The identified up-regulated targets can be modulated with small molecules or antibody-based drugs depending on their druggability. Down-regulated circRNAs can potentially be reconstituted by replacement therapy, whereas up-regulated circRNAs can be inhibited by nucleic acid (NA)-based inhibitors. The validity of the approach of exploring circRNAs and their corresponding targets for therapeutic intervention was underlined by the identification of circRNAs that up-regulate fibroblast growth factor receptors, which can be inhibited by erdafitinib, an approved agent for the treatment of bladder cancer.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 5","pages":"654-682"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12402722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944155","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":"Pioglitazone Suppresses Urothelial Tumorigenesis <i>In Vitro</i>: A Potential Chemopreventive Agent.","authors":"Nguyen Thu Quynh, Yujiro Nagata, Takuo Matsukawa, Eiji Kashiwagi, Naohiro Fujimoto","doi":"10.21873/cgp.20534","DOIUrl":"10.21873/cgp.20534","url":null,"abstract":"<p><strong>Background/aim: </strong>Pioglitazone (PIO), a peroxisome proliferator-activated receptor gamma agonist, is typically used to treat type 2 diabetes mellitus. In addition to its metabolic effects, PIO exhibits various biological activities, including potential anticancer effects. However, its efficacy and mechanistic relevance in the development and progression of cancer, including urothelial carcinoma, remain unclear. Herein, we investigated the functional impact of PIO on urothelial tumorigenesis.</p><p><strong>Materials and methods: </strong>An <i>in vitro</i> urothelial neoplastic transformation model was established by inducing SV-HUC-1 cells with a chemical carcinogen 3-methylcholanthrene. This model was used to investigate the effects of PIO on neoplastic/malignant transformation.</p><p><strong>Results: </strong>PIO significantly inhibited the neoplastic/malignant transformation of SV-HUC-1 cells. Moreover, PIO treatment up-regulated tumor suppressors, including p53 and phosphatase and tensin homolog (PTEN), as well as the epithelial marker E-cadherin, while down-regulating the mesenchymal marker N-cadherin and the oncogenic factor nuclear factor kappa B (NF-κB), as confirmed by protein and mRNA expression analyses.</p><p><strong>Conclusion: </strong>PIO has a chemopreventive effect on urothelial tumorigenesis, supporting its potential use as a preferred anti-diabetic agent for patients with a risk or history of urothelial carcinoma.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 5","pages":"750-759"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12402716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944101","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}