Carcinogenesis最新文献

Urinary Metabolites in Association with Kidney Cancer Risk. 尿代谢产物与肾癌风险的关系

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-06-18 DOI: 10.1093/carcin/bgaf029

Thuraya Al-Sayegh, Shuang Song, Loren Lipworth, Hui Cai, Qing Lan, Yutang Gao, Nathaniel Rothman, Qiuyin Cai, Wei Zheng, Xiao-Ou Shu

{"title":"Urinary Metabolites in Association with Kidney Cancer Risk.","authors":"Thuraya Al-Sayegh, Shuang Song, Loren Lipworth, Hui Cai, Qing Lan, Yutang Gao, Nathaniel Rothman, Qiuyin Cai, Wei Zheng, Xiao-Ou Shu","doi":"10.1093/carcin/bgaf029","DOIUrl":"https://doi.org/10.1093/carcin/bgaf029","url":null,"abstract":"Kidney cancer incidence has increased worldwide in recent decades. While metabolomic studies have shown promise in unveiling mechanisms underlying disease development, few studies have investigated pre-diagnostic urinary metabolites and kidney cancer risk. We conducted a case-control study nested within the Shanghai Women's and Men's Health Studies to prospectively investigate the association between urinary metabolites and kidney cancer risk to understand its etiology and the underlying biological mechanisms. Two hundred primary kidney cancer cases and their individually matched controls were included. A total of 1,301 metabolites were evaluated, and 67 metabolites were found nominally associated with kidney cancer using conditional logistic regression. After backward selection, eleven urine metabolites remained significantly associated with kidney cancer: lipids (e.g., picolinoylglycine, odds ratio (OR); 95% confidence interval (CI): 2.01 [1.44, 2.79], and pregnanediol-3-glucuronide, OR; 95% CI: 0.56 [0.39, 0.82]), xenobiotics (e.g., beta-guanidinopropanoate, OR; 95% CI: 1.75 [1.32, 2.32] and 4-vinylphenol sulfate, OR; 95% CI: 0.66 [0.49, 0.90]), and nucleotides (e.g., allantoic acid, OR; 95% CI: 0.71 [0.54, 0.92]). Time lag analysis showed that metabolite-kidney cancer associations were stronger for beta-guanidinopropanoate (OR; 95%CI: 8.22 [1.68, 40.18]) and picolinoylglycine (OR; 95% CI: 6.45[1.28, 32.43]), but weaker for allantoic acid (OR; 95%CI: 0.87 [0.37, 2.06]) and 3-methylglutarate/2-methylglutarate (OR; 95%CI: 0.62 [0.19, 2.00]) when urinary samples were collected within 3 years between urine sample collection and cancer diagnosis (Pinteraction <0.05 for all). Future metabolomics studies with large sample sizes, particularly from multiple ancestry populations, are needed to validate our findings.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Somatic p53 mutations that are markedly overrepresented in lung cancer confer resistance to ROS-induced cell death. 体细胞p53突变在肺癌中明显过度代表赋予ros诱导的细胞死亡的抗性。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-06-03 DOI: 10.1093/carcin/bgaf027

Mason A Tracewell, Jonathan E Karlin, Samantha M Barnada, Elizabeth L McDuffie, Charles P Scott, Julie A Barta, Steven B McMahon

{"title":"Somatic p53 mutations that are markedly overrepresented in lung cancer confer resistance to ROS-induced cell death.","authors":"Mason A Tracewell, Jonathan E Karlin, Samantha M Barnada, Elizabeth L McDuffie, Charles P Scott, Julie A Barta, Steven B McMahon","doi":"10.1093/carcin/bgaf027","DOIUrl":"https://doi.org/10.1093/carcin/bgaf027","url":null,"abstract":"Lung cancer is among the leading causes of cancer-related death in the U.S. Cigarette smoking remains the leading risk factor for lung cancer and can cause somatic mutations in the critical tumor suppressor gene TP53, among others. Mutations in TP53 not only cause loss of wild-type function but may also introduce oncogenic, gain-of-function (GOF) properties. The frequency of missense mutations at residues p.V157 and p.R158 in p53 increases dramatically in lung cancer relative to other cancers. These p53 mutants exhibit both loss of wild-type p53 function and GOF properties, including broadly rewiring gene expression programs in lung cancer cells. Several pan-cancer hotspot mutations in p53 impart GOF activities that reprogram cellular metabolism. To refine our understanding of the GOF properties conferred by the lung-enriched p53 mutants, the cellular metabolism of cells containing mutant p53 (V157F) was investigated. Untargeted metabolomics revealed that glutathione metabolism is among the top altered metabolic pathways related to mutant p53 (V157F). p53 mutants V157F and R158L provided resistance to oxidative stress induced by both menadione and cigarette smoke extract. The cell death experienced in the absence of mutant p53 (V157F; R158L) was due to the increase in reactive oxygen species (ROS). These findings suggest that the lung-enriched mutations in p53 (V157F; R158L) confer lung cancer cells with resistance to ROS, and ROS accumulation in the absence of mutant p53 causes cell death.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Chemoresistance and immune evasion in hepatocellular carcinoma: the role of miRNA-425-5p. 肝癌化疗耐药和免疫逃逸：miRNA-425-5p的作用。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-03 DOI: 10.1093/carcin/bgaf012

Xinghe Pan, Junliang Liu, Yitong Zhang, Chenglin Sun, You Li

{"title":"Chemoresistance and immune evasion in hepatocellular carcinoma: the role of miRNA-425-5p.","authors":"Xinghe Pan, Junliang Liu, Yitong Zhang, Chenglin Sun, You Li","doi":"10.1093/carcin/bgaf012","DOIUrl":"10.1093/carcin/bgaf012","url":null,"abstract":"Hepatocellular carcinoma (HCC) represents a significant global health challenge, with chemoresistance severely limiting treatment efficacy. This study investigates the role of miRNA-425-5p in exosomes in modulating the tumor microenvironment (TME) and contributing to chemoresistance and immune evasion in HCC. Differentially expressed miRNAs were identified using TaqMan low-density array technology in serum samples from XELOX-resistant and -sensitive HCC patients. miRNA-425-5p expression was validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Exosomes from HCC cell lines were characterized by transmission electron microscopy and nanoparticle tracking analysis. Functional assays, including luciferase reporter assays and flow cytometry, elucidated the mechanisms of miRNA-425-5p. In vivo studies with mouse xenograft models evaluated the impact of miRNA-425-5p on tumor growth and chemosensitivity. miRNA-425-5p was significantly upregulated in the serum of XELOX-resistant HCC patients and correlated with poorer survival outcomes. Exosomes from chemoresistant HCC cells exhibited increased levels of miRNA-425-5p, which, when internalized by CD4+ T cells, promoted regulatory T cell (Treg) expansion by targeting phosphatase and tensin homolog (PTEN). In vivo, miRNA-425-5p overexpression enhanced tumor growth and chemoresistance, while its inhibition reduced tumor size and increased chemosensitivity. These findings indicate that miRNA-425-5p in exosomes plays a crucial role in HCC chemoresistance and immune evasion by modulating the TME and promoting Treg expansion through PTEN targeting. miRNA-425-5p serves as a potential biomarker for predicting chemoresistance and a therapeutic target for overcoming drug resistance in HCC.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

LncRNA MEG3 suppresses prostate cancer progression by mediating macrophage polarization via the miR-148a-3p/ARRDC3 signaling axis. LncRNA MEG3通过miR-148a-3p/ARRDC3信号轴介导巨噬细胞极化抑制前列腺癌进展

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-03 DOI: 10.1093/carcin/bgaf009

Jinguang Luo, Huaixiang Tao, Long Chen, Hao Hu, Likai Mao, Han Guan

{"title":"LncRNA MEG3 suppresses prostate cancer progression by mediating macrophage polarization via the miR-148a-3p/ARRDC3 signaling axis.","authors":"Jinguang Luo, Huaixiang Tao, Long Chen, Hao Hu, Likai Mao, Han Guan","doi":"10.1093/carcin/bgaf009","DOIUrl":"10.1093/carcin/bgaf009","url":null,"abstract":"Long-chain noncoding RNA (LncRNA) MEG3 significantly influences tumor microenvironment (TME) dynamics and macrophage polarization. However, its specific involvement in prostate cancer (PCa) progression remains unclear. MEG3 exhibited low expression in PCa, and immune infiltration analysis revealed a positive association with M1 macrophages infiltration and a negative association with M2 macrophages infiltration. Immunohistochemical analysis demonstrated increased MEG3 levels, corresponding with upregulated INOS (an M1 marker) and downregulated CD163 (an M2 marker). MEG3 expression was markedly elevated in LPS-induced M1 macrophages and notably reduced in IL-4-induced M2 macrophages. The overexpression of MEG3 significantly enhanced M1 macrophages polarization while suppressing M2 macrophages polarization. Using an online database and a dual luciferase reporter assay, miR-148a-3p was identified as a downstream target of MEG3. Reduced miR-148a-3p expression was observed in LPS-induced M1 macrophages, while an increase was noted in IL-4-induced M2 macrophages. Moreover, MEG3 overexpression's impact on macrophage polarization was nullified following miR-148a-3p mimic transfection. ARRDC3 was validated as a downstream target of miR-148a-3p. The upregulation of ARRDC3 triggered by MEG3 overexpression was effectively suppressed by miR-148a-3p mimics. Additionally, Knockdown of ARRDC3 effectively counteracted the MEG3 overexpression-induced increase in M1 macrophages polarization while simultaneously mitigating the reduction in M2 macrophages polarization. Collectively, MEG3 exhibits reduced expression in PCa and correlates with macrophage infiltration and polarization. Specifically, it drives M1 macrophages polarization while suppressing M2 macrophages polarization via the miR-148a-3p/ARRDC3 axis, thereby impeding tumor immune evasion and restricting PCa progression.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Dysregulation of G6PD by HPV E6 exacerbates cervical cancer by activating the STAT3/PLOD2 pathway. HPV E6对G6PD的失调通过激活STAT3/PLOD2通路加重宫颈癌。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-03 DOI: 10.1093/carcin/bgaf005

Jie Zhang, Wei Dong, Qin Yang, Li-Na Liu, Xi-Lun Cai, Dan Wang, Guo-Ji Yan, Yan-Bin Xiyang, Tao Hu, Jie Zhang

{"title":"Dysregulation of G6PD by HPV E6 exacerbates cervical cancer by activating the STAT3/PLOD2 pathway.","authors":"Jie Zhang, Wei Dong, Qin Yang, Li-Na Liu, Xi-Lun Cai, Dan Wang, Guo-Ji Yan, Yan-Bin Xiyang, Tao Hu, Jie Zhang","doi":"10.1093/carcin/bgaf005","DOIUrl":"10.1093/carcin/bgaf005","url":null,"abstract":"High-risk human papillomavirus (HPV) infection is strongly linked to the initiation and progression of cervical cancer (CC), yet the precise molecular mechanisms involved remain partially understood. This investigation examined differential protein expression profiles in various cohorts, including healthy controls and HPV-positive CC patients with different expression levels of glucose-6-phosphate dehydrogenase (G6PD), shedding light on the dysregulation of oncogenic proteins by HPV. Proteomic analysis of cervical tissues revealed specific protein signatures, indicating significant upregulation of HPV E6, G6PD, STAT3, phosphorylated STAT3, and procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) in HPV-infected CC tissues and cell lines. Functional experiments, involving the manipulation of G6PD and STAT3 activities in CC cells with HPV E6 modulation, demonstrated that dysregulated G6PD enhanced cell proliferation, migration, and invasion while suppressing apoptosis, primarily through the STAT3/PLOD2 pathway. Integrating these findings with the existing literature underscores the role of G6PD as an oncogene, potentially under STAT3 regulation, and highlights the role of PLOD2 as a pivotal factor in CC progression. This study also proposed a mechanism in which HPV E6-induced dysregulation of G6PD activates the STAT3-PLOD2 axis to promote CC progression. Understanding the intricate interplay between HPV E6, G6PD, STAT3, and PLOD2 offers valuable insights into the molecular landscape of CC. These findings may pave the way for targeted therapeutic approaches aimed at disrupting this axis to mitigate the progression of CC.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Genetic determinants and clinical significance of circulating and tumor-specific levels of insulin-like growth factor binding protein 7 (IGFBP7) in a Swedish breast cancer cohort. 瑞典乳腺癌队列中胰岛素样生长因子结合蛋白7 （IGFBP7）循环和肿瘤特异性水平的遗传决定因素和临床意义

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-03 DOI: 10.1093/carcin/bgaf020

Christopher Godina, Ann H Rosendahl, Kelin Gonçalves de Oliveira, Somayeh Khazaei, Sofie Björner, Karin Jirström, Karolin Isaksson, Michael N Pollak, Helena Jernström

{"title":"Genetic determinants and clinical significance of circulating and tumor-specific levels of insulin-like growth factor binding protein 7 (IGFBP7) in a Swedish breast cancer cohort.","authors":"Christopher Godina, Ann H Rosendahl, Kelin Gonçalves de Oliveira, Somayeh Khazaei, Sofie Björner, Karin Jirström, Karolin Isaksson, Michael N Pollak, Helena Jernström","doi":"10.1093/carcin/bgaf020","DOIUrl":"https://doi.org/10.1093/carcin/bgaf020","url":null,"abstract":"Previous research indicates that insulin-like growth factor binding protein 7 (IGFBP7) protein levels in breast cancer tissue and blood are prognostic. However, genetic determinants of IGFBP7 in breast cancer remain largely unexplored. We examined IGFBP7 in a cohort of 1701 patients with first breast cancer from Sweden, enrolled prior to surgery 2002-16 and followed for up to 15 years. Genotyping was performed on blood samples using OncoArray. Tumor-specific protein levels of IGFBP7, insulin receptor (InsR), and IGF-I receptor (IGFIR) were assessed on tumor tissue microarrays in 964 patients. Furthermore, 275 patients had plasma IGFBP7 levels measured. A genetic proxy marker for circulating IGFBP7 levels was constructed from five candidate single-nucleotide polymorphisms (SNPs) (rs6852762, rs1714014, rs9992658, rs10004910, and rs4865180) based on number of recessive genotypes. Age-adjusted linear regression was used to evaluate SNPs and tumor-specific IGFBP7 levels in relation to circulating IGFBP7 levels. Cox regression adjusted for age, tumor characteristics, and adjuvant treatments was used to assess associations with clinical outcomes. Circulating and tumor-specific IGFBP7 levels were significantly positively correlated. High circulating and genetically predicted IGFBP7 levels were associated with increased risk for distant metastasis and all-cause mortality. A significant interaction between high tumor-specific IGFBP7 levels and membrane-bound InsR resulted in a four-fold increased risk of breast cancer events and distant metastases. Both measured and genetically predicted IGFBP7 levels were independent prognostic biomarkers in breast cancer.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":"46 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983694","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}

引用次数: 0

Role of the nucleotide excision repair function of CETN2 in the inhibition of the sensitivity of hepatocellular carcinoma cells to oxaliplatin. CETN2核苷酸切除修复功能在抑制肝癌细胞对奥沙利铂敏感性中的作用

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-03 DOI: 10.1093/carcin/bgaf003

Hengcheng Tang, Huaduan Zi, Donghu Zhou, Yanmeng Li, Xiaojin Li, Zhibin Chen, Qianyu Zhu, Qin Ouyang, Pingping He, Sisi Chen, Yanling Li, Jiang Long, Jian Huang

{"title":"Role of the nucleotide excision repair function of CETN2 in the inhibition of the sensitivity of hepatocellular carcinoma cells to oxaliplatin.","authors":"Hengcheng Tang, Huaduan Zi, Donghu Zhou, Yanmeng Li, Xiaojin Li, Zhibin Chen, Qianyu Zhu, Qin Ouyang, Pingping He, Sisi Chen, Yanling Li, Jiang Long, Jian Huang","doi":"10.1093/carcin/bgaf003","DOIUrl":"10.1093/carcin/bgaf003","url":null,"abstract":"Resistance to platinum-based chemotherapy agents like oxaliplatin (OXA) poses significant challenges in the treatment of cancers such as hepatocellular carcinoma (HCC). Centrin 2 (CETN2), which functions in nucleotide excision repair (NER) of DNA damage, is overexpressed in HCC. We investigated the potential role of CETN2 in modulating the sensitivity of HCC cells to OXA. CETN2 expression correlated with decreased OXA sensitivity in Huh7 and Hep3B HCC cell lines. CETN2 forms a complex with XPC, which is crucial for the initial DNA damage recognition in NER, thereby enhancing NER and reducing the efficacy of OXA. siRNA-mediated knockdown of CETN2 increased OXA-induced cytotoxicity and apoptosis, confirming its role in chemoresistance. Moreover, overexpression of CETN2 inhibited OXA-induced DNA damage, an effect partially reversed by XPC knockdown. Our findings highlight CETN2 as a potential biomarker and therapeutic target in overcoming OXA resistance in HCC and suggest the possibility for CETN2 inhibitors in enhancing chemotherapeutic efficacy in the treatment of HCC.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

NUF2 and NEK2 promote malignant progression of gallbladder cancer by remodeling the extracellular matrix. NUF2和NEK2通过重塑细胞外基质促进胆囊癌的恶性进展。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-03 DOI: 10.1093/carcin/bgaf019

Ming Gao, Peng Ye, Yutong Zhang, Yarong Guo, Jun Xu

{"title":"NUF2 and NEK2 promote malignant progression of gallbladder cancer by remodeling the extracellular matrix.","authors":"Ming Gao, Peng Ye, Yutong Zhang, Yarong Guo, Jun Xu","doi":"10.1093/carcin/bgaf019","DOIUrl":"10.1093/carcin/bgaf019","url":null,"abstract":"Gallbladder cancer (GBC) ranks as the most common malignant tumor of the biliary tract, which has been characterized by late diagnosis, low excisional rate, and poor prognosis. Recent studies exploring the roles of malignant progression-associated genes in GBC remain limited. Our study aims to identify significant hub genes involved in its pathogenesis, which may serve as novel potential therapeutic targets for GBC. Here, we employed RNA-seq analysis to identify differentially expressed genes (DEGs) of seven GBC samples and five matched adjacent samples. After screening the DEGs in clinical sequencing data and GSE139682, we further obtained 549 genes with consistent expression trends in two datasets, including 155 upregulated and 394 downregulated genes. Gene Ontology (GO) enrichment analysis revealed that these genes were significantly enriched in extracellular matrix (ECM)-related processes, such as organization, structure, and composition, which hint to us that remodeling of ECM may be the main driving factor for the malignant progression of GBC. In addition, we screened 17 candidate hub genes through protein-protein interaction (PPI) network analysis and Cytoscape, subsequent GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the remodeled ECM mainly functions by affecting cell division. Moreover, we found that NEK2 and NUF2 were overexpressed in GBC tumor tissues and validated their function in the pro-proliferation of GBC cells. Our results highlight that NEK2 and NUF2 may be hub genes promoting the malignant progression of GBC and are expected to be reliable new therapeutic targets for GBC.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12137899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977441","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}

引用次数: 0

Olfactomedin 4 promotes gastric cancer cell G2/M progression and serves as a therapeutic target in gastric adenocarcinoma. Olfactomedin 4促进胃癌细胞G2/M进展，可作为胃腺癌的治疗靶点。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-03 DOI: 10.1093/carcin/bgaf010

Wenli Liu, Hongzhen Li, Istvan Botos, Chutima Kumkhaek, Jianqiong Zhu, Griffin P Rodgers

{"title":"Olfactomedin 4 promotes gastric cancer cell G2/M progression and serves as a therapeutic target in gastric adenocarcinoma.","authors":"Wenli Liu, Hongzhen Li, Istvan Botos, Chutima Kumkhaek, Jianqiong Zhu, Griffin P Rodgers","doi":"10.1093/carcin/bgaf010","DOIUrl":"10.1093/carcin/bgaf010","url":null,"abstract":"Olfactomedin 4 (OLFM4) is a member of the olfactomedin domain-containing olfactomedin glycoprotein family and plays important roles in innate immunity, inflammation, and cancer. It exhibits increased expression in gastric cancer patient tissues and has been shown to regulate proliferation and apoptosis in gastric cancer cells. However, the molecular mechanism(s) underlying OLFM4's role in gastric cancer remain unknown. In this study, we found that OLFM4 knockdown significantly inhibited YCC3 gastric cancer cell proliferation and induced G2/M cell cycle arrest. Yeast two-hybridization screening revealed that OLFM4 directly interacts with cyclin B1 interacting protein 1 (CCNB1IP1), an E3 ubiquitin protein ligase. In YCC3 cells, OLFM4 co-immunoprecipitated and colocalized with CCNB1IP1 and underwent cell cycle phase-specific nucleo-cytoplasmic shuttling. OLFM4 knockdown decreased both cyclin B1 protein levels and CDK1 activity in YCC3 cells. Screening of a cohort of OLFM4-targeted microRNAs (miRNAs) for their impact on cell proliferation identified several that significantly downregulated OLFM4 protein levels and inhibited YCC3 cell proliferation in vitro. Rescue experiments demonstrated that these miRNAs' inhibitory effect on cell proliferation was partially related to their downregulation of OLFM4. When three of these miRNAs were individually administered intratumorally to nude mice bearing YCC3 cell xenografts, tumor growth was significantly inhibited when compared with tumors treated with a negative control miRNA. These results suggest that OLFM4 promotes cell cycle progression and cell proliferation in gastric cancer cells and may have utility as a therapeutic target in gastric adenocarcinoma.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582186","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}

引用次数: 0

Current challenges and potential opportunities for interception and prevention of head and neck cancer. 当前的挑战和潜在的机会拦截和预防头颈癌。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-03 DOI: 10.1093/carcin/bgaf025

Karam El-Bayoumy, Neil Christensen, James Broach, Craig Meyers, Douglas Stairs, Mitchell Machtay, Jiafen Hu, Zachary T Bitzer, Todd D Schell, Kun-Ming Chen, Yuan-Wan Sun, Dhimant Desai, Vonn Walter, Junjia Zhu

{"title":"Current challenges and potential opportunities for interception and prevention of head and neck cancer.","authors":"Karam El-Bayoumy, Neil Christensen, James Broach, Craig Meyers, Douglas Stairs, Mitchell Machtay, Jiafen Hu, Zachary T Bitzer, Todd D Schell, Kun-Ming Chen, Yuan-Wan Sun, Dhimant Desai, Vonn Walter, Junjia Zhu","doi":"10.1093/carcin/bgaf025","DOIUrl":"10.1093/carcin/bgaf025","url":null,"abstract":"Globally, the incidence of head and neck squamous cell carcinoma (HNSCC) has increased over recent decades and is projected to continue to rise, largely driven by increases in oropharyngeal squamous cell carcinoma (OPSCC), which is linked to HPV infection. HPV infection is also involved in the development of other cancers (anogenital and cervical), and almost 100% of cervical cancer patients are positive for HPV. OPSCC is the most common HPV-associated cancer in men and has exceeded the incidence of cervical cancer cases in women in the USA. Our knowledge of the carcinogenesis process from HPV infection to OPSCC development has been primarily extrapolated from cervical cancer models. While the cooperation of tobacco smoking and HPV infection is documented in cervical cancer, mechanistic studies to address this interaction in management and control of HNSCC are scarce and are also extrapolated from cervical cancer models. The molecular heterogeneity of HNSCC constitutes a tremendous challenge, and despite advances in several fronts in the management and control of HNSCC, short- and long-term treatment-associated morbidities remain substantial. In addition to deaths directly caused by this disease, survivors of this cancer have the second-highest rate of suicide compared with other cancers survivors. Given the existing gaps in our knowledge and the current clinical challenges, future studies including a number of new conceptual and methodological elements discussed in this review can lead to the discovery of biomarkers for early detection of the disease and novel strategies that will advance our knowledge to intercept and prevent HNSCC.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092900","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}

引用次数: 0