Carcinogenesis最新文献

{"title":"The emerging roles of noncoding RNAs in cancer.","authors":"Akanksha Samuel, George A Calin","doi":"10.1093/carcin/bgag053","DOIUrl":"10.1093/carcin/bgag053","url":null,"abstract":"<p><p>Noncoding RNAs (ncRNAs) regulate gene expression through transcriptional, post-transcriptional, and epigenetic mechanisms, shaping hallmarks of cancer, including metastasis, therapy resistance, and relapse. Carcinogenesis arises when aberrant ncRNA networks initiate malignant transformation and sustain oncogenic changes through epigenetic modifications, shifts in cell identity, failures in genome protection, metabolic changes, and alterations in the tumour microenvironment. Environmental exposures, combined with chronic inflammation, reorganize these networks early on, leading to the formation of premalignant fields and persistent epigenetic changes. The four major ncRNA classes, microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and PIWI-interacting RNAs (piRNAs) function as either oncogenes or tumour suppressors depending on the specific cancer type. Their stability, cell-type-specific expression, and presence in biofluids make them suitable candidates for biomarker discovery and liquid biopsy applications. Therapeutic strategies now include antisense oligonucleotides, small interfering RNAs, synthetic miRNA mimics, RNA aptamers, and aptamer-siRNA conjugates, which can either inhibit oncogenic ncRNAs or restore tumour-suppressive regulatory networks. CRISPR-based ncRNA modulation, including Cas9-mediated locus editing, CRISPR interference/activation, and Cas13-mediated transcript targeting, remains largely investigational because delivery, off-target activity, and an incomplete understanding of ncRNA context dependence continue to limit translation. High-throughput sequencing, single-cell transcriptomics, and computational modelling have accelerated the identification of cancer-related ncRNAs and elucidated their biological functions. This review examines how different types of ncRNAs contribute to cancer initiation, progression, and treatment resistance, and assesses their potential as diagnostic markers, prognostic factors, and therapeutic targets.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13583532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849839","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":"Exposure to per-and polyfluoroalkyl substances and early-onset cancers.","authors":"Maaike van Gerwen, Mathilda Monaghan, Alexandra Boni, Melissa Florentino Puello, Lauren M Petrick, Angela M Leung","doi":"10.1093/carcin/bgag051","DOIUrl":"https://doi.org/10.1093/carcin/bgag051","url":null,"abstract":"<p><p>Environmental exposures, such as per-and polyfluoroalkyl substances (PFAS), are suspected to play a role in the significant increase in incidence of some early-onset cancers. PFAS are chemicals of concern due to their persistence in the environment, long biological half-lives, and potential carcinogenic properties. Exposure during sensitive windows of development may exert durable effects on cancer-related biological pathways leading to greater risks of early-onset cancers. This review summarizes the current evidence of PFAS exposure and early-onset carcinogenesis, with an emphasis on potential exposure routes, early-onset cancer development in humans linked with PFAS exposure, and mechanistic pathways. Emerging evidence supports a potential role for PFAS exposure in carcinogenesis during early life, particularly through prenatal and early postnatal windows of susceptibility. While epidemiologic studies increasingly link PFAS to several types of cancer, the evidence specifically addressing early-onset cancers remains limited and heterogeneous. Future research should prioritize prospective, longitudinal cohort studies with repeated exposure measurements spanning prenatal, infancy, and childhood periods, coupled with long-term follow-up into early adulthood to capture early-onset cancer outcomes.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":"47 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103922","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}

{"title":"ADH1B-ALDH2 genotype combinations, age-related risk, and field cancerization in head and neck and upper GI cancer screening in 10 073 alcohol-dependent men.","authors":"Akira Yokoyama, Tai Omori, Tetsuji Yokoyama","doi":"10.1093/carcin/bgag034","DOIUrl":"10.1093/carcin/bgag034","url":null,"abstract":"<p><p>We analyzed initial endoscopic screening results, including esophageal iodine staining and oropharyngolaryngeal inspection, from 10 073 Japanese alcohol-dependent men (30-79 years) between 1993 and 2025. After adjustment for age, drinking and smoking habits, and screening year, using ADH1B*2 (rs1229984) plus ALDH2*1/*1 as the reference, the cancer risk (odds ratio (OR) [95% confidence interval (CI)]) associated with slow-metabolizing ADH1B*1/*1 plus ALDH2*1/*1, ADH1B*2 plus inactive ALDH2*2 (rs671), and ADH1B*1/*1 plus ALDH2*2 increased synergistically: 3.06 (2.13-4.39), 10.2 (7.33-14.2), and 21.0 (14.5-30.3) for esophageal squamous cell carcinoma (ESCC; n = 309, detection rate 3.1%); 4.34 (2.24-8.41), 11.3 (5.99-21.4), and 27.4 (14.3-52.5) for head and neck squamous cell carcinoma (HNSCC; n = 95, 0.9%). ADH1B*2 plus ALDH2*2 increased the OR for gastric adenocarcinoma (GA) to 3.71 (2.19-6.30; n = 91, 0.9%). ESCC and HNSCC were already detected at ages 30-39 (ESCC 0.3%, HNSCC 0.6%) and 40-49 (ESCC 1.3%, HNSCC 0.5%), and the corresponding ORs were markedly high in the 30-49 age group: 12.1 (2.62-56.0), 20.5 (4.09-103), and 166 (37.9-730) for ESCC; and 11.8 (1.36-102), 26.4 (2.92-238), and 95.0 (11.5-786) for HNSCC. The age-gradient difference in ORs was significant for ESCC (P = .008). ORs by genotype combination did not differ significantly across screening-year periods or by invasive status. Multiple cancers were detected in 39.8% of ESCC, 52.6% of HNSCC, and 30.8% of GA. Inactive ALDH2*2 was consistently linked with cancer multiplicity: ESCC OR 2.96 (1.77-4.95), HNSCC OR 14.0 (3.93-49.8), and GA OR 5.41 (1.63-18.0). These results support genotype-informed public health interventions in heavy-drinking East Asian populations.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101084","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}

{"title":"Microplastics in early-onset carcinogenesis.","authors":"Anne M Bailey, Lorne J Hofseth","doi":"10.1093/carcin/bgaf093","DOIUrl":"10.1093/carcin/bgaf093","url":null,"abstract":"<p><p>Plastics have become integral to modern life, but their persistence has generated vast quantities of microplastics (MPs, <5 mm) and nanoplastics (NPs, <1 µm) that now contaminate food, water, air, and human tissues. Although not yet classified as carcinogens by the International Agency for Research on Cancer, accumulating experimental and epidemiologic evidence raises concern that MPs may contribute to cancer development. Global plastic production has risen from 2 megatons in 1950 to >450 megatons annually in 2022, leaving behind pervasive waste that fragments into MPs and NPs. These particles act as xenobiotics, carrying toxic additives and adsorbed pollutants, provoking oxidative stress, chronic inflammation, DNA damage, and microbiome disruption, all processes central to carcinogenesis. MPs have been detected in human cancers, and animal studies show tissue accumulation, fibrosis, and genomic instability following exposure. Importantly, the proliferation of plastics parallels a global rise in early-onset cancers (diagnosed before age 50), suggesting a possible, though unproven, temporal association. Individuals born after the 1950s plastic boom have experienced continuous MP exposure beginning in utero, potentially predisposing them to carcinogenic pathways later in life. In this review, we integrate human biomonitoring data, experimental findings, and clinical observations to evaluate the emerging hypothesis that chronic MP exposure contributes to cancer risk. While causality has not been established, the biological plausibility and mounting evidence underscore the urgent need for mechanistic and epidemiologic studies to clarify the role of MPs and NPs in cancer development. It also underscores an urgent need for research into causal pathways and preventive mechanisms.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951570","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":"TGF-β1 and TGF-β2 family members differentially modulate tumor initiation and invasiveness of primary liver cancer in a MMP14-dependent manner.","authors":"Darko Castven, Sharon Pereira, Luis Z Rodriguez, Merle E Fischer, Federico Marini, Steven Dooley, Henrike Salié, Johann von Felden, Lina Jegodzinski, Nadja M Meindl-Beinker, Ju-Seog Lee, Peter R Galle, Jens U Marquardt","doi":"10.1093/carcin/bgag037","DOIUrl":"https://doi.org/10.1093/carcin/bgag037","url":null,"abstract":"<p><p>Emerging evidence suggests that perturbation of TGF-β signaling in parenchymal cells drives malignant transformation and cancer progression in a subset of patients with primary liver cancer (PLC). TGF-β plays a crucial role in liver pathophysiology with diverse effects on various processes and cell types. In liver homeostasis, TGF-β signaling exerts tumor-suppressive functions that are often lost during carcinogenic transformation, when downstream signaling rebranches from tumor-suppressive to pro-tumorigenic, facilitating invasiveness and metastasis. In this study, primary patient-derived and established liver cancer cell lines were exposed to TGF-β1 and TGF-β2, and effects on tumor-initiating potential, invasion, and migration were assessed by in vitro analyses including colony/sphere formation and wound healing assays. RNA sequencing and reverse-phase protein array (RPPA) were employed to analyze differential gene and protein expression across treatments. Our findings demonstrate that TGF-β1 and TGF-β2 reduced proliferation, colony and spheroid formation in investigated cell lines. Notably, TGF-β1 increased migratory and invasive properties of both HCC and CCA cell lines, whereas TGF-β2 had no such effect. Transcriptome profiling revealed activation of gene sets associated with cell cycle regulation by both ligands. Pro-migratory effects of TGF-β1 were linked to epithelial-mesenchymal transition (EMT), including enrichment of matrix metalloproteinase (MMP) and actin cytoskeleton pathways. Specifically, TGF-β1 downregulated epithelial marker E-cadherin and upregulated mesenchymal markers Vimentin and SNAIL. RPPA indicated p21 induction by both ligands, causing cell cycle arrest, while TGF-β1 specifically upregulated MMP14, promoting EMT-related properties. In conclusion, targeting TGF-β1-MMP14-EMT pathway could complement TGF-β-based therapies in PLC management.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155446","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}

{"title":"Correction: Arenobufagin, a natural bufadienolide from toad venom, induces apoptosis and autophagy in human hepatocellular carcinoma cells through inhibition of PI3K/Akt/mTOR pathway.","authors":"","doi":"10.1093/carcin/bgag035","DOIUrl":"https://doi.org/10.1093/carcin/bgag035","url":null,"abstract":"","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":"47 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216585","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}

{"title":"Correction to: Hypoxia-increased RAGE and P2X7R expression regulates tumor cell invasion through phosphorylation of Erk1/2 and Akt and nuclear translocation of NF-κB.","authors":"","doi":"10.1093/carcin/bgag033","DOIUrl":"https://doi.org/10.1093/carcin/bgag033","url":null,"abstract":"","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":"47 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216598","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}

{"title":"Current progress of CDC20 in cancer development and targeting CDC20 for cancer therapy.","authors":"Yingtong Chen, Shuang Gao, Ping Yang, Shuozi Liu, Weilong Zhang, Jing Wang, Hongmei Jing","doi":"10.1093/carcin/bgag021","DOIUrl":"10.1093/carcin/bgag021","url":null,"abstract":"<p><p>Cell division cycle 20 homolog (CDC20), a critical substrate-recruiting subunit of the anaphase-promoting complex/cyclosome (APC/C), binds to APC/C to form the active APC/C-CDC20 complex, which regulates the degradation of key cell cycle substrates to ensure accurate and timely mitotic progression. Accumulating evidence demonstrates that CDC20 functions as an oncogenic factor, with its overexpression observed in various malignancies. Its dysregulation is closely associated with tumor initiation, progression, drug resistance, and poor clinical outcomes, underscoring its potential as a therapeutic target in anti-cancer strategies. In this review, we describe the biological functions of CDC20 in cancers, discuss its role and underlying mechanisms in solid tumors and hematological malignancies, and elucidate currently reported CDC20-targeted inhibitors along with their clinical benefits and challenges. By emphasizing the oncogenic significance of CDC20, we propose that the development of specific, safe, and potent CDC20 inhibitors could provide a promising therapeutic approach for cancer patients exhibiting CDC20 overexpression.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509851","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}

{"title":"Stromal NNMT overexpression as an independent prognostic biomarker in lung adenocarcinoma and breast carcinoma.","authors":"Yanzhong Wang, Yiping Wu, Shuyang Zheng, Xiaotian Yan, Xingtong Yu, Yuzhen Gao, Shuduo Xie, Zhinong Jiang, Rui An, Guoli Li, Jun Yang, Qingchao Tong, Xinyou Xie, Jun Zhang","doi":"10.1093/carcin/bgag020","DOIUrl":"10.1093/carcin/bgag020","url":null,"abstract":"<p><p>This study investigated the expression profile and prognostic significance of nicotinamide N-methyltransferase (NNMT) in pan-cancer stroma, with focused validation in lung adenocarcinoma (LUAD) and breast carcinoma (BC). Integrated analysis of Genotype-Tissue Expression and The Cancer Genome Atlas databases revealed tumor-specific NNMT mRNA upregulation in these malignancies. Subsequently, the relationship between NNMT mRNA expression levels and clinical parameters across multiple cancer types was examined, with particular emphasis on LUAD, BC, and CRC. Single-cell RNA sequencing data further revealed elevated NNMT expression specifically within stromal compartments, with fibroblasts exhibiting the highest NNMT expression levels among stromal cell populations. Protein-level validation using the Human Protein Atlas database, the National Cancer Institute's Proteomics Data Commons, and the quantitative immunohistochemistry of our independent clinical cohorts demonstrated elevated stromal NNMT protein expression, particularly in cancer-associated fibroblasts. Cox regression analysis and survival curve analysis established stromal NNMT expression as an independent prognostic factor for overall survival in LUAD and BC patients (P < .05). In conclusion, high stromal NNMT levels correlated with poor prognosis, establishing it as a promising biomarker for risk stratification in LUAD and BC.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13174943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580245","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":"Retraction: \"The Bmi-1 polycomb protein antagonizes the (-)-epigallocatechin-3-gallate-dependent suppression of skin cancer cell survival\".","authors":"","doi":"10.1093/carcin/bgag027","DOIUrl":"https://doi.org/10.1093/carcin/bgag027","url":null,"abstract":"","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":"47 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027331","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}