Carcinogenesis最新文献_第4页

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

Inhibition of benzo[a]pyrene-induced DNA adduct in buccal cells of smokers by black raspberry lozenges. 黑覆盆子润喉糖抑制吸烟者口腔细胞中苯并[a]芘诱导的 DNA 加合物

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae067

Kun-Ming Chen, Nicolle M Krebs, Yuan-Wan Sun, Dongxiao Sun, Jiangang Liao, Lisa Reinhart, Jacek Krzeminski, Shantu Amin, Gary Stoner, Susan R Mallery, Karam El-Bayoumy

{"title":"Inhibition of benzo[a]pyrene-induced DNA adduct in buccal cells of smokers by black raspberry lozenges.","authors":"Kun-Ming Chen, Nicolle M Krebs, Yuan-Wan Sun, Dongxiao Sun, Jiangang Liao, Lisa Reinhart, Jacek Krzeminski, Shantu Amin, Gary Stoner, Susan R Mallery, Karam El-Bayoumy","doi":"10.1093/carcin/bgae067","DOIUrl":"10.1093/carcin/bgae067","url":null,"abstract":"Using LC-MS/MS analysis we previously showed for the first time (Carcinogenesis 43:746-753, 2022) that levels of DNA damage induced by benzo[a]pyrene (B[a]P), an oral carcinogen and tobacco smoke (TS) constituent, were significantly higher in buccal cells of smokers than those in nonsmokers; these results suggest the potential contribution of B[a]P in the development of oral squamous cell carcinoma (OSCC) in humans. Treating cancers, including OSCC, at late stages, even with improved targeted therapies, continues to be a major challenge. Thus interception/prevention remains a preferable approach for OSCC management and control. In previous preclinical studies, we and others demonstrated the protective effects of black raspberry (BRB) against carcinogen-induced DNA damage and OSCC. Thus, to translate preclinical findings, we tested the hypothesis in a Phase 0 clinical study that BRB administration reduces DNA damage induced by B[a]P in the buccal cells of smokers. After enrolling 27 smokers, baseline buccal cells were collected before the administration of BRB lozenges (5/day for 8 weeks, 1 gm BRB powder/lozenge) at baseline, at the middle and the end of BRB administration. The last samples were collected 4 weeks after BRB cessation (washout period). B[a]P-induced DNA damage (BPDE-N2-dG) was evaluated by LC-MS/MS. BRB administration resulted in a significant reduction in DNA damage: 26.3% at the midpoint (P = .01506) compared to baseline, 36.1% at the end of BRB administration (P = .00355), and 16.6% after BRB cessation (P = .007586). Our results suggest the potential benefits of BRB as a chemopreventive agent against the development of TS-initiated OSCC.","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/PMC11886790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379126","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

Inhibition of phospholipase D1 reduces pancreatic carcinogenesis in mice partly through a FAK-dependent mechanism. 抑制磷脂酶 D1 可部分通过 FAK 依赖性机制减少小鼠胰腺癌的发生。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae071

Hala A Addassi, Irena Krga, Fernando Villarreal, Joseph F LaComb, Michael A Frohman, Karen Matsukuma, Gerardo G Mackenzie

{"title":"Inhibition of phospholipase D1 reduces pancreatic carcinogenesis in mice partly through a FAK-dependent mechanism.","authors":"Hala A Addassi, Irena Krga, Fernando Villarreal, Joseph F LaComb, Michael A Frohman, Karen Matsukuma, Gerardo G Mackenzie","doi":"10.1093/carcin/bgae071","DOIUrl":"10.1093/carcin/bgae071","url":null,"abstract":"Phospholipase D (PLD) plays a critical role in cancer progression. However, its role in pancreatic cancer remains unclear. Thus, we evaluated the role of PLD1, one of two classical isoforms of PLD, in pancreatic carcinogenesis in vivo. The role of PLD1 in tumor growth was evaluated by subcutaneously transplanting human MIA PaCa-2 cells expressing endogenous PLD1 levels (Ctr KD cells) or cells in which PLD1 was knocked down (Pld1 KD cells) into immunodeficient mice. Twenty days post-implantation, tumors that arose from Pld1-KD cells were significantly smaller, compared to controls (Ctr KD). Then, we assessed the role of PLD1 in the tumor microenvironment, by subcutaneously implanting mouse LSL-KrasG12D/+;Trp53R172H/+;Pdx-1-Cre (KPC) cells into wild-type or PLD1 knockout (Pld1-/-) mice. Compared to wild type, tumor growth was attenuated in Pld1-/- mice by 39%, whereas treatment of Pld1-/- mice with gemcitabine reduced tumor growth by 79%. When PLD1 was ablated in LSL-KrasG12D;Ptf1Cre/+ (KC) mice, no reduction in acinar cell loss was observed, compared to KC mice. Finally, treatment of KC mice with a small molecule inhibitor of PLD1 and PLD2 (FIPI) significantly reduced acinar cell loss and cell proliferation, compared to vehicle-treated mice. Mechanistically, the effect of PLD on tumor growth is mediated, partly, by the focal adhesion kinase pathway. In conclusion, while PLD1 is a critical regulator of pancreatic xenograft and allograft growth, playing an important role at the tumor and at the microenvironment levels, the inhibition of PLD1 and PLD2 is necessary to reduce pancreatic carcinogenesis in KC mice and might represent a novel therapeutic target.","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":"142564080","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

SMARCA4/BRG1 deficiency induces a targetable dependence on oxidative phosphorylation in clear cell renal cell carcinoma. 在透明细胞肾细胞癌中，SMARCA4/BRG1缺陷诱导氧化磷酸化的可靶向依赖性。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgaf002

Ru Fang, Xiaotong Wang, Ruina Wu, Rui Pan, Miaomiao Tian, Rusong Zhang, Xue Wei, Xuan Wang, Shengbing Ye, Feng Li, Qiuyuan Xia, Yang Cheng, Qiu Rao

{"title":"SMARCA4/BRG1 deficiency induces a targetable dependence on oxidative phosphorylation in clear cell renal cell carcinoma.","authors":"Ru Fang, Xiaotong Wang, Ruina Wu, Rui Pan, Miaomiao Tian, Rusong Zhang, Xue Wei, Xuan Wang, Shengbing Ye, Feng Li, Qiuyuan Xia, Yang Cheng, Qiu Rao","doi":"10.1093/carcin/bgaf002","DOIUrl":"10.1093/carcin/bgaf002","url":null,"abstract":"The tumor suppressor gene SMARCA4, a critical component of the SWI/SNF chromatin remodeling complex, is frequently inactivated in various cancers, including clear cell renal cell carcinoma (ccRCC). Despite its significance, the role of SMARCA4 in ccRCC development and its potential therapeutic vulnerabilities have not been fully explored. Our research found that SMARCA4 deficiency was associated with poor prognosis and was observed in a subset of high-grade ccRCCs. Through functional assays, we determined that the suppression of SMARCA4 led to an increase in RCC cell proliferation. Further gene expression analysis unveiled that SMARCA4-deficient cells exhibit an upregulation of the oxidative phosphorylation (OXPHOS) pathway. Delving deeper, we combined RNA sequencing (RNA-Seq) and Assay for transposase-accessible chromatin with sequencing (ATAC-Seq) data to uncover that SMARCA4 plays a crucial role in modulating chromatin accessibility and the expression of genes essential for the respiratory electron transport chain. A significant finding from our study is that RCC cells and xenograft tumors lacking SMARCA4 demonstrated an increased sensitivity to the inhibition of the OXPHOS pathway by the novel small molecule IACS-010759. This sensitivity is attributed to the heightened energy demands and susceptibility to energy stress observed in SMARCA4-deficient cells, driven by their amplified biosynthetic requirements. The efficacy of IACS-010759 stems from its ability to induce energy deprivation, pinpointing OXPHOS inhibition as a promising therapeutic approach for targeting SMARCA4-mutant tumors. This strategy offers a novel avenue to address a currently unmet therapeutic need, highlighting the potential of OXPHOS inhibition in the treatment of cancers harboring SMARCA4 mutations.","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":"143032311","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

Ubiquitin-specific peptidase 49 promotes adenocarcinoma of the esophagogastric junction malignant progression via activating SHCBP1-β-catenin-GPX4 axis. USP49 通过激活 SHCBP1-β-catenin-GPX4 轴促进食管胃交界处腺癌的恶性发展。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae060

Yun Ding, Zhen Liu, Xiaofeng Dai, Ruiwen Ruan, Hongguang Zhong, Zhipeng Wu, Yangyang Yao, Jun Chen, Jun Deng, Jianping Xiong

{"title":"Ubiquitin-specific peptidase 49 promotes adenocarcinoma of the esophagogastric junction malignant progression via activating SHCBP1-β-catenin-GPX4 axis.","authors":"Yun Ding, Zhen Liu, Xiaofeng Dai, Ruiwen Ruan, Hongguang Zhong, Zhipeng Wu, Yangyang Yao, Jun Chen, Jun Deng, Jianping Xiong","doi":"10.1093/carcin/bgae060","DOIUrl":"10.1093/carcin/bgae060","url":null,"abstract":"Adenocarcinoma of the esophagogastric junction (AEG) has received widespread attention because of its increasing incidence. However, the molecular mechanism underlying tumor progression remains unclear. Here, we report that the downregulation of ubiquitin-specific peptidase 49 (USP49) promotes ferroptosis in OE33 and OE19 cells, thereby inhibiting cell proliferation in vitro and in vivo, whereas the overexpression of USP49 had the opposite effect. In addition, USP49 downregulation promoted AEG cell radiotherapy sensitivity. Moreover, overexpression of Glutathione PeroXidase 4 reversed the ferroptosis and proliferation inhibition induced by USP49 knockdown. Mechanistically, USP49 deubiquitinates and stabilizes Shc SH2-domain-binding protein 1, subsequently facilitating the entry of β-catenin into the nucleus to enhance Glutathione PeroXidase 4 transcriptional expression. Finally, high USP49 expression was correlated with shorter overall survival in patients with AEG. In summary, our findings identify USP49 as a novel regulator of ferroptosis in AEG cells, indicating that USP49 may be a potential therapeutic target in AEG.","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":"142131937","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

Advanced glycation end products promote the progression of endometrial cancer via activating the RAGE/CHKA/PI3K/AKT signaling pathway. 高级糖化终末产物通过激活 RAGE/CHKA/PI3K/AKT 信号通路促进子宫内膜癌的进展。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae059

Wan Shu, Teng Hua, Xiaoyan Xin, Jun Zhang, Jing Lin, Rui Shi, Rong Zhao, Wei Zhang, Ke-Jun Dong, Hongbo Wang, Xing Zhou

{"title":"Advanced glycation end products promote the progression of endometrial cancer via activating the RAGE/CHKA/PI3K/AKT signaling pathway.","authors":"Wan Shu, Teng Hua, Xiaoyan Xin, Jun Zhang, Jing Lin, Rui Shi, Rong Zhao, Wei Zhang, Ke-Jun Dong, Hongbo Wang, Xing Zhou","doi":"10.1093/carcin/bgae059","DOIUrl":"10.1093/carcin/bgae059","url":null,"abstract":"Endometrial cancer (EC) is a common malignant tumor that is closely associated with metabolic disorders such as diabetes and obesity. Advanced glycation end products (AGEs) are complex polymers formed by the reaction of reducing sugars with the amino groups of biomacromolecules, mediating the occurrence and development of many chronic metabolic diseases. Recent research has demonstrated that the accumulation of AGEs can affect the tumor microenvironment, metabolism, and signaling pathways, thereby affecting the malignant progression of tumors. However, the mechanism by which AGEs affect EC is unclear. Our research aimed to investigate how AGEs promote the development of EC through metabolic pathways and to explore their potential underlying mechanisms. Our experimental results demonstrated that AGEs upregulated the choline metabolism mediated by choline kinase alpha (CHKA) through the receptor for advanced glycation end products, activating the PI3K/AKT pathway and enhancing the malignant biological behavior of EC cells. Virtual screening and molecular dynamics simulation revealed that timosaponin A3 could target CHKA to inhibit AGE-induced progression of EC and that a newly discovered CHKA inhibitor could be a novel targeted inhibitor for the treatment of EC. This study provides new therapeutic strategies and contributes to the treatment of EC.","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":"142046408","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

Epigenetic mechanisms underlying endometrial cancer outcomes: race-specific patterns of DNA methylation associated with molecular subtypes and survival. 子宫内膜癌（EC）预后的表观遗传机制：与分子亚型和生存相关的DNA甲基化的种族特异性模式

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgaf004

Emery Hoos, Lauren E Koval, David L Corcoran, Lauren A Eaves, Kyle Roell, Julia E Rager, Xianming Tan, Sherette Godfrey, Temitope O Keku, Victoria Bae-Jump, Andrew F Olshan, Hazel B Nichols, Bernard E Weissman, Rebecca C Fry

{"title":"Epigenetic mechanisms underlying endometrial cancer outcomes: race-specific patterns of DNA methylation associated with molecular subtypes and survival.","authors":"Emery Hoos, Lauren E Koval, David L Corcoran, Lauren A Eaves, Kyle Roell, Julia E Rager, Xianming Tan, Sherette Godfrey, Temitope O Keku, Victoria Bae-Jump, Andrew F Olshan, Hazel B Nichols, Bernard E Weissman, Rebecca C Fry","doi":"10.1093/carcin/bgaf004","DOIUrl":"10.1093/carcin/bgaf004","url":null,"abstract":"Endometrial cancer (EC) is the fourth most common cancer in women in the USA. Stark racial disparities are present in EC outcomes in which Black women have significantly higher EC-related mortality than White women. The social and biologic factors that contribute to these disparities are complex and may include racial differences in epigenetic landscapes. To investigate race-specific epigenetic differences in EC tumor characteristics and outcomes, we utilized the most recent data within the Cancer Genome Atlas (TCGA). Genome-wide CpG methylation data for more than 850 000 CpG sites were analyzed across 245 tumor samples, including 52 from Black women and 181 from White women. Race-adjusted and race-stratified associations among CpG methylation in ECs and molecular subtypes and disease-free survival were examined. Race-specific analysis identified subtype-associated CpGs within 9572 genes in tumors from White women and only 10 genes in tumors that were from Black women. Race-specific analyses also identified survival-associated CpGs with 1119 unique genes identified in tumors from White women and none identified in tumors from Black women. Genes identified with differential methylation among subtypes included those involved in oxidative stress (HIF3A), and DNA repair (MLH1). Data from a replication cohort highlighted genes overlapping with those identified within the TCGA, such as G Protein Subunit Beta 1 (GNB1), involved in G-protein signaling, and Interleukin 37 (IL37), involved in cytokine signaling. Identification of these racial differences in EC tumor epigenetic landscapes and associated changes in gene expression may provide insight into strategies to improve outcomes and reduce disparities.","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/PMC11894373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051743","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