Carcinogenesis最新文献_第3页

Multifaceted role of transgelin isoforms in cancer hallmarks. transgelin异构体在癌症标志中的多方面作用。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-03 DOI: 10.1093/carcin/bgaf014

Ana Maria Jimenez Jimenez, Yazan Haddad, Vendula Jemelikova, Vojtech Adam, Miguel Angel Merlos Rodrigo

{"title":"Multifaceted role of transgelin isoforms in cancer hallmarks.","authors":"Ana Maria Jimenez Jimenez, Yazan Haddad, Vendula Jemelikova, Vojtech Adam, Miguel Angel Merlos Rodrigo","doi":"10.1093/carcin/bgaf014","DOIUrl":"10.1093/carcin/bgaf014","url":null,"abstract":"Transgelins (TAGLNs) are actin-binding proteins within the calponin family, playing a crucial role in modulating actin-myosin interactions and maintaining actin filament stability. These proteins are expressed in both smooth and non-smooth muscle cells, contributing to the regulation of muscle contractility and cell migration. TAGLNs family has three isoforms that differ in their isoelectric point, namely: TAGLN1, TAGLN2, and TAGLN3. TAGLNs regulation is involved in the development of many diseases, such as pulmonary arterial hypertension, asthma, atherosclerosis, obstructive nephropathy, diabetes, and cancer. Recent research indicates TAGLNs involvement in carcinogenesis and chemoresistance. This review investigates TAGLNs as potential cancer biomarkers, exploring their versatile tissue-specific impact on patient outcomes. We also highlight their roles as, tumor suppressor agents and tumor progression oncogenes depending on the tumor type, tumor genetic variations, and TAGLNs expression profiles. Furthermore, emerging evidence suggests that the interplay between TAGLN2 and chemoresistance to anticancer drugs is mediated by its interaction with the chemoresistance double agent MT-2, with possible bidirectional implications. TAGLNs present a promising avenue for novel therapeutic strategies against cancer, owing to their tissue-specific duality in promoting/suppressing tumor growth and cell migration in cancer cells. Thus, they can serve as a potential prognostic/diagnostic biomarker. The focus should be on leveraging, in future therapeutics, the interplay between TAGLNs and MTs to reverse tumor progression and chemoresistance, transforming them into tumor suppression.","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":"143656152","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

Amlodipine, an L-type Ca2+ channel inhibitor, regulates release of extracellular vesicles from tumor cells. 氨氯地平是一种l型Ca2+通道抑制剂，可调节肿瘤细胞外囊泡的释放。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-03 DOI: 10.1093/carcin/bgaf016

Sujan K Mondal, Chang-Sook Hong, Jie Han, Brenda Diergaarde, Dan P Zandberg, Theresa L Whiteside

{"title":"Amlodipine, an L-type Ca2+ channel inhibitor, regulates release of extracellular vesicles from tumor cells.","authors":"Sujan K Mondal, Chang-Sook Hong, Jie Han, Brenda Diergaarde, Dan P Zandberg, Theresa L Whiteside","doi":"10.1093/carcin/bgaf016","DOIUrl":"10.1093/carcin/bgaf016","url":null,"abstract":"Tumor cells produce/release tumor-derived exosomes (TEX) which promote tumor growth, drive immune suppression, and interfere with immune therapies. Amlodipine, a calcium flux inhibitor, may block TEX release by tumor cells. Amlodipine's potential as a drug blocking TEX release was evaluated. We measured tumor growth, TEX numbers, phenotype, and molecular content in murine SCCVII and human cancer cell lines. Cell lysates and TEX were tested for expression of autophagy-related proteins by western blots (WBs). Tumor growth in mice, histopathology, T-cell infiltrations, and TEX production by SCCVII treated with amlodipine were measured. Numbers and protein content of TEX eluted from tumor explants were studied by flow cytometry and WBs. Amlodipine used in vitro at 0.5-5 µM was nontoxic, did not impair tumor cell viability, reduced cell proliferation, and decreased TEX production. It reduced PD-L1 and Rab11 content of TEX, altered tumor cell size/shape, induced vesicle accumulations in the cytosol, and upregulated expression levels of autophagy-related proteins, ATG7, Beclin-1, and LC3. In vivo, daily treatment of established SCCVII with amlodipine (10 mg/kg) inhibited tumor growth (P < 0.001), increased CD8+ T-cell infiltration into tumor, decreased TEX production, and altered PD-L1, Rab11, and FasL content of TEX. Amlodipine delivered in vitro to tumor cells or in vivo to tumor-bearing mice interferes with tumor growth and TEX production, induces tumor autophagy, reduces circulating TEX numbers, and alters the TEX immunosuppressive signature. Amlodipine emerges as a potentially promising drug for removing immunosuppressive TEX in cancer subjects who are candidates for immune therapies.","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/PMC12096003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691306","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

Reactions of [13C]-labelled tobacco smoke with DNA to generate selected adducts formed without metabolic activation. [13C]标记的烟草烟雾与DNA反应生成未经代谢激活形成的选定加合物。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-03 DOI: 10.1093/carcin/bgaf008

Mei-Kuen Tang, Trevor Ostlund, Nour F Dameh, Aleksandra Alcheva, Jerry D Cohen, Adrian D Hegeman, Steven G Carmella, Irina Stepanov, Stephen S Hecht

{"title":"Reactions of [13C]-labelled tobacco smoke with DNA to generate selected adducts formed without metabolic activation.","authors":"Mei-Kuen Tang, Trevor Ostlund, Nour F Dameh, Aleksandra Alcheva, Jerry D Cohen, Adrian D Hegeman, Steven G Carmella, Irina Stepanov, Stephen S Hecht","doi":"10.1093/carcin/bgaf008","DOIUrl":"10.1093/carcin/bgaf008","url":null,"abstract":"DNA adducts are central in the carcinogenic process because they can cause miscoding leading to permanent mutations in important genes involved in carcinogenesis. While it is known that tobacco smoking leads to increased levels of multiple DNA adducts, most DNA adducts detected to date in humans cannot be explicitly attributed to smoking but instead have various possible exogenous and endogenous sources. We plan to probe the tobacco source of DNA adducts by providing carbon-13 labelled ([13C]-labelled) cigarettes to smokers and analyzing [13C]-labelled DNA adducts in their oral cells to determine which adducts arise from smoking. Prior to conducting studies in humans, we first report here proof-of-principle machine smoking experiments to evaluate carbon isotopologues of (a) selected carbonyls and (b) DNA adducts resulting from direct exposure of cigarette smoke vapour-phase to calf-thymus DNA. The smoke of the study cigarettes, made from a 50:50 mixture of [13C]-labelled tobacco and a popular commercial tobacco, yielded similar concentrations of carbonyl compounds and their respective DNA adducts compared with the smoke of 1R6F reference cigarettes and the popular brand of cigarettes. We detected [13C]-isotopologues of DNA adducts such as 1,N6-etheno-dA, (8R/S)-3-(2'-deoxyribos-1-yl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a]purine-10(3H)-one (γ-OH-Acr-dG), and (6S,8S and 6R,8R)-3-(2'-deoxyribos-1-yl)-5,6,7,8-tetrahydro-8-hydroxy-6-methylpyrimido[1,2-a]purine-10(3H)-one [(6S,8S)-γ-OH-Cro-dG and (6R,8R)-γ-OH-Cro-dG], proving that they have a direct source from tobacco smoke and providing important new insights regarding their mechanisms of formation. These unique results form the basis for further studies in cell culture and in cigarette smokers to establish how carcinogens in tobacco smoke cause DNA adduct formation.","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/PMC12035816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555943","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

Delta 4-desaturase sphingolipid 2 enhances prostate cancer stem-like traits through phytoceramide-mediated PI3K-AKT signaling pathway. 德尔塔4-去饱和酶鞘脂2通过植物神经酰胺介导的PI3K-AKT信号通路增强前列腺癌茎样性状。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-03 DOI: 10.1093/carcin/bgaf024

Yuanyuan Luo, Jiachuan Yu, Qi Li, Xiaolin Wang, Xinyu Liu, Guowang Xu, Wangshu Qin

{"title":"Delta 4-desaturase sphingolipid 2 enhances prostate cancer stem-like traits through phytoceramide-mediated PI3K-AKT signaling pathway.","authors":"Yuanyuan Luo, Jiachuan Yu, Qi Li, Xiaolin Wang, Xinyu Liu, Guowang Xu, Wangshu Qin","doi":"10.1093/carcin/bgaf024","DOIUrl":"10.1093/carcin/bgaf024","url":null,"abstract":"Cancer stem cells (CSCs) are the initiating cells of tumorigenesis, metastasis, and recurrence and play a crucial role in androgen deprivation therapy resistance, yet how sphingolipid metabolism promotes CSC maintenance remains exclusive. Here, we conducted gene expression profiling of sphere-derived castration-resistant prostate cancer stem cells (PCSCs) and identified enhanced sphingolipid de novo biosynthesis with upregulated DEGS2 expression in PCSCs. Silencing of DEGS2 significantly suppressed prostate cancer stem-like traits, cell growth, clonogenicity, and metastasis, while ectopic overexpression of DEGS2 showed the opposite effects. Mechanistically, DEGS2-synthesized phytoceramide activates PI3K-AKT signaling pathway to promote cancer stem-like characteristics, and activation of AKT reversed DEGS2-depletion-inhibited cancer stem-like properties. Clinically, prostate cancer tissues expressed higher levels of DEGS2 compared with adjacent normal tissue, and DEGS2 expression exhibits strong correlations with SOX2, CD133, and Snail expression in primary prostate carcinomas. Collectively, our data illustrate that DEGS2 dictates prostate cancer stem-like properties via the PI3K-AKT pathway, and disruption of this pathway provides potential therapeutic strategies for prostate cancer.","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":"144086063","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

B vitamins and colorectal cancer: exploring research hotspots and frontiers from a bibliometric and visual analysis (1994-2024). B族维生素与结直肠癌：从文献计量学和视觉分析探索研究热点和前沿（1994-2024）。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-03 DOI: 10.1093/carcin/bgaf021

Meichen Li, Lingshi Meng, Hong Gu, Yuan Tian, Boyang Qu, Yanrong Ao, Xingyang Chen, Yuan Song, Weiwei Cui

{"title":"B vitamins and colorectal cancer: exploring research hotspots and frontiers from a bibliometric and visual analysis (1994-2024).","authors":"Meichen Li, Lingshi Meng, Hong Gu, Yuan Tian, Boyang Qu, Yanrong Ao, Xingyang Chen, Yuan Song, Weiwei Cui","doi":"10.1093/carcin/bgaf021","DOIUrl":"10.1093/carcin/bgaf021","url":null,"abstract":"Most studies suggest that B vitamins can reduce the risk of colorectal cancer (CRC), and research in this field has been growing. Focusing on 2617 articles in the field, this study used CiteSpace and VOSviewer software to evaluate the contributions of various countries/regions, institutions, authors, and journals. The United States and Harvard University were identified as the most productive nation and institution, respectively, with Edward L. Giovannucci (Harvard) being the top contributor. Cancer Epidemiology Biomarkers & Prevention was recognized as the leading journal. Through the analysis of keywords and citations, we found that the potential of B vitamins (B1, B2, B6, B9, and B12) in the prevention and treatment of CRC and their mechanisms including regulation of gene expression, anti-inflammatory and antioxidant, and modulation of gut microenvironment are hot topics of research in this field. Burst detection analysis further revealed that the application of nanoparticle-based targeted drug delivery systems (such as folate-conjugated nanocarriers) in the treatment of CRC represents both a current hotspot and a future trend. This study offers a comprehensive overview of the field, highlights research hotspots and trends, and offers valuable information for researchers to further grasp the research direction.","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":"143959236","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

Identification of HCAR1 as a ferroptosis-related biomarker of gastric cancer based on a novel ferroptosis-related prognostic model and in vitro experiments. 基于新型吸铁相关预后模型和体外实验的HCAR1作为胃癌吸铁相关生物标志物的鉴定

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-03 DOI: 10.1093/carcin/bgaf030

Hongjiao Zhang, Jinbo Zhan, Juanjuan Zhou, Liping Liu, Yan He, Yi Le, Weiqi Liu, Ling Zhou, Yawen Liu, Xiaojun Xiang

{"title":"Identification of HCAR1 as a ferroptosis-related biomarker of gastric cancer based on a novel ferroptosis-related prognostic model and in vitro experiments.","authors":"Hongjiao Zhang, Jinbo Zhan, Juanjuan Zhou, Liping Liu, Yan He, Yi Le, Weiqi Liu, Ling Zhou, Yawen Liu, Xiaojun Xiang","doi":"10.1093/carcin/bgaf030","DOIUrl":"10.1093/carcin/bgaf030","url":null,"abstract":"Currently, research on ferroptosis-related prognostic models for gastric cancer is limited, whereas traditional predictive models often have a narrow perspective and low accuracy. In this study, we systematically analyzed the expression patterns of ferroptosis-related genes in patients with gastric adenocarcinoma and evaluated their prognostic value. Using data from The Cancer Genome Atlas (TCGA) and the FerrDb database, we developed a ferroptosis-related prognostic risk model based on four genes: hydroxycarboxylic acid receptor 1 (HCAR1), branched-chain amino acid transaminase 1 (BCAT1), ceruloplasmin (CP), and dickkopf-1 (DKK1). This model demonstrated strong prognostic value and potential clinical relevance in stratifying gastric cancer patients by overall survival outcomes. ferroptosis-related prognostic risk model. Compared to traditional clinicopathological features, the risk score derived from this model exhibited superior predictive accuracy for overall survival in patients with gastric cancer and served as an independent prognostic factor. Functional enrichment analysis revealed that the risk score was primarily enriched for extracellular matrix-related pathways. Additionally, the risk score was significantly correlated with TME signature genes, immune checkpoint expression, and immune cell infiltration in stomach adenocarcinoma (STAD). Mechanistic studies revealed that HCAR1 is abnormally overexpressed in gastric cancer tissues and is associated with a poor prognosis. It exerted its effects by regulating the GPX4/SLC7A11 axis to inhibit lipid peroxidation and malondialdehyde accumulation, thereby obstructing ferroptosis. Experimental validation demonstrated that the downregulation of HCAR1 promoted ferroptosis and suppressed malignant tumor phenotypes, suggesting that both the gene and its associated risk model hold significant clinical value as potential therapeutic targets and prognostic biomarkers.","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":"144246612","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 susceptibility to lung squamous cell carcinoma: new insights on 9q33.2 variants and tobacco smoking. 肺鳞状细胞癌的遗传易感性：关于 9q33.2 变异和吸烟的新见解。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-03 DOI: 10.1093/carcin/bgaf018

Huimin Ma, Guoqing Wang, Sunan Miao, Chen Jin, Jiaying Cai, Wenjing Ge, Chang Zhang, Erbao Zhang, Hongxia Ma, Meng Zhu

{"title":"Genetic susceptibility to lung squamous cell carcinoma: new insights on 9q33.2 variants and tobacco smoking.","authors":"Huimin Ma, Guoqing Wang, Sunan Miao, Chen Jin, Jiaying Cai, Wenjing Ge, Chang Zhang, Erbao Zhang, Hongxia Ma, Meng Zhu","doi":"10.1093/carcin/bgaf018","DOIUrl":"10.1093/carcin/bgaf018","url":null,"abstract":"Genome-wide association studies (GWAS) have identified over 60 susceptibility loci for lung cancer, yet the biological mechanisms underlying these associations remain largely unknown, particularly for lung squamous cell carcinoma (LUSC). Here, we integrated data from 3890 LUSC cases and 13 328 controls of Chinese descent, and performed a conditional analysis to explore independent genetic variants and analyzed the interaction between the genetic variants and smoking. Our study was the first to identify a specific association between genetic variants in the 9q33.2 region and increased risk of LUSC in smokers. After adjusting for the tag SNP rs4573350 in 9q33.2, no additional significant genetic variants were found. However, significant additive (RERI = 1.66, 95% CI: 1.17-2.22, AP = 0.26, 95% CI: 0.19-0.33) and multiple interactions (OR = 1.30, 95% CI: 1.08-1.56, P = 5.40 × 10-3) were observed between rs4573350 and smoking. Compared to nonsmokers with the CC genotype, smokers with the CT/TT genotype showed an increased risk of 6.29-fold (95% CI: 5.46-7.23, P = 2.00 × 10-16). Functional annotation identified rs4573350 as the strongest functional variant within the linkage disequilibrium block. Biological experiments confirmed that the combined exposure to the T allele of rs4573350 and cigarette smoke extract promotes the expression of the ZBTB26 by modulating the binding ability of the transcription factor FOXA1. Furthermore, ZBTB26 was found to regulate tumorigenesis of LUSC both in vitro and in vivo by affecting the expression of PCNA, which is involved in cell cycle and promotes tumorigenesis of LUSC.","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":"143762903","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

Establishing a new-onset diabetes-related metabolism signature for predicting the prognosis and immune landscape in pancreatic cancer. 建立新发糖尿病相关代谢特征，用于预测胰腺癌的预后和免疫状况。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-04-03 DOI: 10.1093/carcin/bgae072

Yilei Yang, Luyao Liu, Haochen Cui, Bin Cheng, Wang Peng, Ronghua Wang, Jinlin Wang, Wei Chen, Mengdie Cao, Yanling Li, Jingwen Liang, Shiru Chen, Shuya Bai, Yuchong Zhao

{"title":"Establishing a new-onset diabetes-related metabolism signature for predicting the prognosis and immune landscape in pancreatic cancer.","authors":"Yilei Yang, Luyao Liu, Haochen Cui, Bin Cheng, Wang Peng, Ronghua Wang, Jinlin Wang, Wei Chen, Mengdie Cao, Yanling Li, Jingwen Liang, Shiru Chen, Shuya Bai, Yuchong Zhao","doi":"10.1093/carcin/bgae072","DOIUrl":"10.1093/carcin/bgae072","url":null,"abstract":"New-onset diabetes (NOD) is a common condition among patients with pancreatic adenocarcinoma (PAAD) and is related to poor clinical outcomes. The potential impact of NOD on PAAD progression and the tumor microenvironment remains unclear. Here, we revealed that NOD in PAAD was associated with metabolic disorders. Utilizing three machine-learning algorithms, an NOD-related metabolism signature (NRMS) was established. Validated in three independent cohorts, patients with a high NRMS score exhibited a worse prognosis. Moreover, an elevated NRMS score was associated with an immunosuppressive microenvironment and diminished response to immunotherapy. Further experiments demonstrated that ALDH3A1, a key feature in NRMS, was significantly upregulated in tissues from PAAD patients with NOD and played a crucial role in tumor progression and immune suppression. Our findings highlight the potential of NRMS as a prognostic biomarker and an indicator of immunotherapy response for patients with PAAD.","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/PMC11966386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615485","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

Integrative functional screen of genomic loci uncovers CCND2 and its genetic regulatory mechanism in colorectal cancer development. 基因组位点综合功能筛选揭示CCND2及其在结直肠癌发生中的遗传调控机制

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae078

Bin Li, Mei Wu, Hui Geng, Yan Li, Zhirui Chen, Zequn Lu, Xu Chen, Qiuhong Wang, Shuxin Song, Xiangpan Li, Xu Zhu, Yongchang Wei, Ying Zhu, Xiaoping Miao, Jianbo Tian, Jiuyang Liu, Chaoqun Huang, Xiaojun Yang

{"title":"Integrative functional screen of genomic loci uncovers CCND2 and its genetic regulatory mechanism in colorectal cancer development.","authors":"Bin Li, Mei Wu, Hui Geng, Yan Li, Zhirui Chen, Zequn Lu, Xu Chen, Qiuhong Wang, Shuxin Song, Xiangpan Li, Xu Zhu, Yongchang Wei, Ying Zhu, Xiaoping Miao, Jianbo Tian, Jiuyang Liu, Chaoqun Huang, Xiaojun Yang","doi":"10.1093/carcin/bgae078","DOIUrl":"10.1093/carcin/bgae078","url":null,"abstract":"Although genome-wide association studies have identified dozens of loci associated with colorectal cancer (CRC) susceptibility, the causal genes or risk variants within these loci and their biological functions often remain elusive. Recently, the genomic locus 12p13.32, with the tag single-nucleotide polymorphism rs10774214, was identified as a crucial CRC risk locus in Asian populations. However, the functional mechanism of this region has not been fully elucidated. Here, we applied a high-throughput RNA interference approach in CRC cell lines to interrogate the function of genes in this genomic region. Multiple genes were found to affect cell functions, with CCND2 having the most significant effect as an oncogene. Moreover, overexpressed CCND2 could promote CRC cell proliferation. Subsequently, by integrating a fine-mapping analysis and multi-ancestry large-scale population cohorts consisting of 14 358 CRC cases and 34 251 healthy controls, we identified a regulatory variant rs4477507-T that contributed to an increased CRC risk in populations from China (odds ratio = 1.16, 95% confidence interval = 1.11-1.22, P = 4.45 × 10-10) and Europe (odds ratio = 1.17, 95% confidence interval = 1.12-1.21, P = 1.65 × 10-14). Functional characterization of the variant demonstrated that it could act as an allele-specific enhancer to distally facilitate the expression of CCND2 mediated by the transcription factor TEAD4. Overall, our study underscores the essential role of CCND2 in CRC development and delineates its regulatory mechanism mediated by rs4477507, establishing an epidemiological and biological link between genetic variation and CRC pathogenesis.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827500","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

Systematic assessment of serum i-tRF-AsnGTT in gastric cancer: a potential clinical biomarker. 胃癌血清 i-tRF-AsnGTT 系统评估：一种潜在的临床生物标记物

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae044

Xiaodan Jiang, Xun Li, Yang Li, Yu Zhang, Xinliang Gu, Wei Zong, Xianjuan Shen, Shaoqing Ju

{"title":"Systematic assessment of serum i-tRF-AsnGTT in gastric cancer: a potential clinical biomarker.","authors":"Xiaodan Jiang, Xun Li, Yang Li, Yu Zhang, Xinliang Gu, Wei Zong, Xianjuan Shen, Shaoqing Ju","doi":"10.1093/carcin/bgae044","DOIUrl":"10.1093/carcin/bgae044","url":null,"abstract":"Since gastric cancer (GC) shows no apparent signs in its early stages, most patients are diagnosed later with a poor prognosis. We therefore seek more sensitive and specific GC biomarkers. Small RNAs formed from tRNAs represent a novel class of non-coding RNAs that are highly abundant in bodily fluids and essential to biological metabolism. This study explores the potential of i-tRF-AsnGTT in gastric cancer diagnostics. To begin with, we sequenced i-tRF-AsnGTT using high-throughput methods. i-tRF-AsnGTT expression levels in GC were determined using real-time fluorescence polymerase chain reaction. Agarose gel electrophoresis, Sanger sequencing, and repeated freezing and thawing were performed to verify molecular properties. A correlation was found between clinical and pathological parameters and i-tRF-AsnGTT expression levels through the χ2 test, and receiver operating characteristic was used to analyze its diagnostic value in GC. In serum, i-tRF-AsnGTT has a low and stable expression level. It can differentiate between patients with gastric cancer and gastritis and healthy donors with better diagnostic efficacy. In combination with clinicopathological parameters, i-tRF-AsnGTT correlates with tumor differentiation; infiltration depth of tumors; tumor, node, metastasis stage; lymph node metastases; and neural/vascular invasion. Serum i-tRF-AsnGTT expression is low in GC patients. Serum from postoperative patients shows increased i-tRF-AsnGTT expression levels. Potentially, this could be used as a biomarker to help diagnose gastric cancer and monitor its prognosis.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632698","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