Carcinogenesis最新文献_第7页

HuR/miR-124-3p/VDR complex bridges lipid metabolism and tumor development in colorectal cancer. HuR/miR-124-3p/VDR复合物是结直肠癌脂质代谢和肿瘤发生的桥梁。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae061

Fengxing Huang, Luping Bu, Mengting Li, Youwei Wang, Runan Zhang, Yu Shao, Kun Lin, Hong Yang, Qiu Zhao, Lan Liu

{"title":"HuR/miR-124-3p/VDR complex bridges lipid metabolism and tumor development in colorectal cancer.","authors":"Fengxing Huang, Luping Bu, Mengting Li, Youwei Wang, Runan Zhang, Yu Shao, Kun Lin, Hong Yang, Qiu Zhao, Lan Liu","doi":"10.1093/carcin/bgae061","DOIUrl":"10.1093/carcin/bgae061","url":null,"abstract":"Maintaining a balanced lipid status to prevent lipotoxicity is of paramount importance in various tumors, including colorectal cancer (CRC). HuR, an RNA-binding protein family member, exhibits high expression in many cancers possibly because it regulates cell proliferation, migration, invasion, and lipid metabolism. However, the role of HuR in the regulation of abnormal lipid metabolism in CRC remains unknown. We found that HuR promotes vitamin D receptor (VDR) expression to ensure lipid homeostasis by increasing triglyceride (TG) and total cholesterol (TC) levels in CRC, thus confirming the direct binding of an overexpressed HuR to the CDS and 3'-UTR of Vdr, enhancing its expression. Concurrently, HuR can indirectly affect VDR expression by inhibiting miR-124-3p. HuR can suppress the expression of miR-124-3p, which binds to the 3'-UTR of Vdr, thereby reducing VDR expression. Additionally, a xenograft model demonstrated that targeting HuR inhibits VDR expression, blocking TG and TC formation, and hence mitigating CRC growth. Our findings suggest a regulatory relationship among HuR, miR-124-3p, and VDR in CRC. We propose that the HuR/miR-124-3p/VDR complex governs lipid homeostasis by impacting TG and TC formation in CRC, offering a potential therapeutic target for CRC prevention and treatment.","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":"142104642","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

Yes-associated protein plays oncogenic roles in human sporadic colorectal adenomas. yes相关蛋白（YAP）在人类散发性结直肠腺瘤中起致瘤作用。

IF 2.9 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgaf007

Lei Fan, Xingyi Guo, Mary K Washington, Jiajun Shi, Reid M Ness, Qi Liu, Wanqing Wen, Shuya Huang, Xiao Liu, Qiuyin Cai, Wei Zheng, Robert J Coffey, Martha J Shrubsole, Timothy Su

{"title":"Yes-associated protein plays oncogenic roles in human sporadic colorectal adenomas.","authors":"Lei Fan, Xingyi Guo, Mary K Washington, Jiajun Shi, Reid M Ness, Qi Liu, Wanqing Wen, Shuya Huang, Xiao Liu, Qiuyin Cai, Wei Zheng, Robert J Coffey, Martha J Shrubsole, Timothy Su","doi":"10.1093/carcin/bgaf007","DOIUrl":"10.1093/carcin/bgaf007","url":null,"abstract":"The role of Hippo-Yes-associated protein (YAP) in human colorectal cancer (CRC) presents contradictory results. We examined the function of YAP in the early stages of CRC by quantitatively measuring the expression of phospho-YAPS127 (p-YAP) and five APC-related proteins in 145 sporadic adenomas from the Tennessee Colorectal Polyp Study, conducting APC sequencing for 114 adenomas, and analyzing YAP-correlated cancer pathways using gene expression data from 326 adenomas obtained from Gene Expression Omnibus. The p-YAP expression was significantly correlated with YAP expression (r = 0.53, P < .0001) and nuclear β-catenin (r = 0.26, P = .0018) in adenoma tissues. Both p-YAP and nuclear β-catenin were associated with APC mutations (P = .05). A strong association was observed between p-YAP overexpression and advanced adenoma odds (OR = 12.62, 95% CI = 4.57-34.86, P trend < .001), which persisted after adjusting for covariates and biomarkers (OR = 12.31, 95% CI = 3.78-40.10, P trend < .0001). P-YAP exhibited a sensitivity of 77.4% and specificity of 78.2% in defining advanced versus nonadvanced adenomas. Additionally, synergistic interaction was noted between p-YAP positivity and nuclear β-catenin on advanced adenomas (OR = 16.82, 95% CI = 4.41-64.08, P < .0001). YAP-correlated genes were significantly enriched in autophagy, unfolded protein response, and sirtuin pathways showing predominantly pro-tumorigenic alterations. Collectively, YAP plays an oncogenic role in interacting with Wnt as well as other cancer pathways within human sporadic adenomas. P-YAP could be a potential biomarker for human high-risk sporadic adenomas.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467167","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

Germline alteration analysis reveals EPHB4R91H mutation as a key player in multiple primary lung tumors. 种系畸变分析揭示 EPHB4R91H 突变是多种原发性肺肿瘤的关键因素

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae074

Jing Li, Yanan Li, Xinjuan Wang, Zhigang Zhou, Xiangnan Li, Songwei Yue, Huaqi Wang, Ming Yang, Guojun Zhang

{"title":"Germline alteration analysis reveals EPHB4R91H mutation as a key player in multiple primary lung tumors.","authors":"Jing Li, Yanan Li, Xinjuan Wang, Zhigang Zhou, Xiangnan Li, Songwei Yue, Huaqi Wang, Ming Yang, Guojun Zhang","doi":"10.1093/carcin/bgae074","DOIUrl":"10.1093/carcin/bgae074","url":null,"abstract":"Multiple primary lung tumors are garnering attention from clinicians, with adenocarcinoma emerging as the predominant histological type. Because of the heterogeneity and diffuse distribution of lesions in the same patient, the treatment of multiple primary lung adenocarcinoma (MPLA) is a significant challenge. As a kind of variation unaffected by tumor heterogeneity, germline alterations may play a key role in the development of MPLA. Here, whole-exome sequencing of peripheral blood was employed to obtain germline alteration data. Intergroup comparative analyses on rare and deleterious alterations of MPLA, solitary lung adenocarcinoma, and healthy individuals in an MPLA family were performed to clarify the candidate alterations. Whole-exome sequencing and targeted Sanger sequencing were performed in 27 disseminated MPLA patients to detect the mutation site that had been screened. A rare and deleterious germline alteration, EPHB4R91H, was found in all of the patients of an MPLA family and a patient with disseminated MPLA. It was revealed that EPHB4R91H was able to enhance the proliferation, migration, and invasion ability of A549 cells through increased binding affinity to ephrinB2, which in turn activated the EPHB4/ERK/JNK/MAPK pathway. Our findings corroborate that germline alterations are involved in the development of MPLA. And it was found for the first time that the EPHB4R91H mutation promotes the development of MPLA by enhancing its affinity for ephrinB2 and thereby active EPHB4/ERK/JNK/MAPK pathway.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686222","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

The role of interleukin 17 in cancer: a systematic review. 白细胞介素 17 (IL17) 在癌症中的作用：系统综述。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae079

Emir Begagic, Semir Vranic, Ajith Sominanda

引用次数: 0

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae080

Pu Yang, Qian Yu

{"title":"Immune-related genes for the prediction of response to imatinib therapy in chronic myeloid leukemia.","authors":"Pu Yang, Qian Yu","doi":"10.1093/carcin/bgae080","DOIUrl":"10.1093/carcin/bgae080","url":null,"abstract":"Chronic myeloid leukemia (CML) is a malignant hyperplastic tumor that originates from pluripotent hematopoietic stem cells in the bone marrow. The introduction of tyrosine kinase inhibitors has significantly improved the survival rates of CML patients. This study aimed to identify immune-related genes associated with the response to imatinib (IM) therapy in CML. Gene expression profiles from IM-treated CML patients were obtained from the Gene Expression Omnibus database and categorized into high- and low-score groups based on immune scores calculated using the ESTIMATE algorithm. Subsequent bioinformatics analysis identified 428 differentially expressed immune-related genes in the CML context. Functional enrichment analysis revealed that these genes were involved in immune-related pathways, including T-cell receptor signaling and cytokine-cytokine receptor interaction. Finally, based on five modules in weighted gene co-expression network analysis and the top-ranked degree, 10 hub genes were identified. Receiver operating characteristic analysis in two Gene Expression Omnibus datasets identified IL10RA, SCN9A, and SLC26A11 as potential biomarkers for predicting IM response. We further validated these biomarkers in an independent clinical cohort of 60 CML patients treated with IM. Results from quantitative real-time polymerase chain reaction (qRT-PCR) revealed high expression of IL10RA and SLC26A11 in responders, while SCN9A showed low expression. All three genes had an area under the curve greater than 0.75, confirming their potential as predictive biomarkers. These findings deepen our understanding of functional characteristics and immune-related molecular mechanisms underlying IM response and offer promising predictive biomarkers.","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":"142876351","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

Testicular sex cord-stromal tumors in mice with constitutive activation of PI3K and loss of Pten. PI3K组成性激活和Pten缺失小鼠睾丸性索间质肿瘤。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae077

Marija Dinevska, Lachlan McAloney, Samuel S Widodo, Gulay Filiz, Jeremy Anderson, Sebastian Dworkin, Simon P Windley, Dagmar Wilhelm, Theo Mantamadiotis

{"title":"Testicular sex cord-stromal tumors in mice with constitutive activation of PI3K and loss of Pten.","authors":"Marija Dinevska, Lachlan McAloney, Samuel S Widodo, Gulay Filiz, Jeremy Anderson, Sebastian Dworkin, Simon P Windley, Dagmar Wilhelm, Theo Mantamadiotis","doi":"10.1093/carcin/bgae077","DOIUrl":"10.1093/carcin/bgae077","url":null,"abstract":"Testicular tumors are the most common malignancy of young men, and tumors affecting the testis are caused by somatic mutations in germ or germ-like cells. The PI3K pathway is constitutively activated in about one-third of testicular cancers. To investigate the role of the PI3K pathway in transforming stem-like cells in the testis, we investigated tumors derived from mice with post-natal, constitutive activation of PI3K signaling and homozygous deletion of tumor suppressor Pten, targeted to Nestin-expressing cells. Mice developed aggressive tumors, exhibiting heterogeneous histopathology and hemorrhaging. The tumors resemble the rare testis tumor type, testicular sex cord-stromal Leydig cell tumors. Single-cell resolution spatial tissue analysis demonstrated that T-cells are the dominant tumor-infiltrating immune cell type, with very few infiltrating macrophages observed in the tumor tissue, with CD8+ T-cells predominating. Further analysis showed that immune cells preferentially localize to, or accumulate within stromal regions.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821937","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

The ‌BCL2-associated athanogene-3-Interferon-induced transmembrane protein 2 axis enhances pancreatic ductal adenocarcinoma growth via the Mitogen-activated protein kinase signaling pathway. BAG3-IFITM2 轴通过 MAPK 信号通路促进胰腺导管腺癌生长

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-12-30 DOI: 10.1093/carcin/bgae053

Peipei Wang, Congliang Chen, Kexin Lin, Yu Zhang, Junmei Hu, Tongbo Zhu, Xia Wang

{"title":"The ‌BCL2-associated athanogene-3-Interferon-induced transmembrane protein 2 axis enhances pancreatic ductal adenocarcinoma growth via the Mitogen-activated protein kinase signaling pathway.","authors":"Peipei Wang, Congliang Chen, Kexin Lin, Yu Zhang, Junmei Hu, Tongbo Zhu, Xia Wang","doi":"10.1093/carcin/bgae053","DOIUrl":"10.1093/carcin/bgae053","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy, exhibits escalating incidence and mortality rates, underscoring the urgent need for the identification of novel therapeutic targets and strategies. The BCL2-associated athanogene-3 (BAG3) protein, a multifunctional regulator involved in various cellular processes, notably plays a crucial role in promoting tumor progression and acts as a potential \"bridge\" between tumors and the tumor microenvironment. In this study, we demonstrate that PDAC cells secrete BAG3 (sBAG3), which engages the interferon-induced transmembrane protein 2 (IFITM2) receptor to activate the mitogen-activated protein kinase signaling pathway, specifically enhancing phospho-extracellular regulated protein (pERK) activity, thereby propelling PDAC growth. Furthermore, our preliminary investigation into the effects of sBAG3 on co-cultured natural killer cells intriguingly discovered that sBAG3 diminishes natural killer cell cytotoxicity and active molecule expression. In conclusion, our findings confirm the pivotal role of the sBAG3-IFITM2 axis in fostering PDAC progression, highlighting the potential significance of sBAG3 as a dual therapeutic target for both tumor and immune cells.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"928-939"},"PeriodicalIF":3.3,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104643","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

Population dynamics is a cancer driver. 人口动态是癌症的驱动因素。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-12-30 DOI: 10.1093/carcin/bgae038

Mariana Dos Santos Oliveira, Marcelo de C Griebeler, Bernardo Henz, Filipe Ferreira Dos Santos, Gabriela D A Guardia, Helena B Conceição, Pedro A F Galante, Darlan C Minussi, Manuel M Oliveira, Guido Lenz

{"title":"Population dynamics is a cancer driver.","authors":"Mariana Dos Santos Oliveira, Marcelo de C Griebeler, Bernardo Henz, Filipe Ferreira Dos Santos, Gabriela D A Guardia, Helena B Conceição, Pedro A F Galante, Darlan C Minussi, Manuel M Oliveira, Guido Lenz","doi":"10.1093/carcin/bgae038","DOIUrl":"10.1093/carcin/bgae038","url":null,"abstract":"Most tissues are continuously renovated through the division of stem cells and the death of old or damaged cells, which is known as the cell turnover rate (CTOR). Despite being in a steady state, tissues have different population dynamics thus producing diverse clonality levels. Here, we propose and test that cell population dynamics can be a cancer driver. We employed the evolutionary software esiCancer to show that CTOR, within a range comparable to what is observed in human tissues, can amplify the risk of a mutation due to ancestral selection (ANSEL). In a high CTOR tissue, a mutated ancestral cell is likely to be selected and persist over generations, which leads to a scenario of elevated ANSEL profile, characterized by few niches of large clones, which does not occur in low CTOR. We found that CTOR is significantly associated with the risk of developing cancer, even when correcting for mutation load, indicating that population dynamics per se is a cancer driver. This concept is central to understanding cancer risk and for the design of new therapeutic interventions that minimizes the contribution of ANSEL in cancer growth.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":"893-902"},"PeriodicalIF":3.3,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261092","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

Antitumor activity of niclosamide-mediated oxidative stress against acute lymphoblastic leukemia. 烟酰胺介导的氧化应激对急性淋巴细胞白血病的抗肿瘤活性。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-12-30 DOI: 10.1093/carcin/bgae035

Jing Yang, Yong Liu, Zefan Du, Qin Zhou, Luo Yang, Qianyun Ye, Jingxuan Pan, Waiyi Zou, Chun Chen, Bei Jin

引用次数: 0

Editor-in-Chief's Note-Thank you to Reviewers. 总编辑注：感谢审稿人。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-12-30 DOI: 10.1093/carcin/bgae076

引用次数: 0