Molecular Carcinogenesis最新文献_第7页

NEK2 Promotes ESCC Malignant Progression by Inhibiting Cellular Senescence via the FOXM1/c-Myc/p27 Signaling Pathway. NEK2 通过 FOXM1/c-Myc/p27 信号通路抑制细胞衰老，从而促进 ESCC 恶性进展。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-02-01 Epub Date: 2024-11-06 DOI: 10.1002/mc.23839

Jiachen Li, Yaojie Wang, Sisi Wei, Shi Xu, Suli Dai, Li Zhang, Ziqiang Tian, Lianmei Zhao, Huilai Lv

{"title":"NEK2 Promotes ESCC Malignant Progression by Inhibiting Cellular Senescence via the FOXM1/c-Myc/p27 Signaling Pathway.","authors":"Jiachen Li, Yaojie Wang, Sisi Wei, Shi Xu, Suli Dai, Li Zhang, Ziqiang Tian, Lianmei Zhao, Huilai Lv","doi":"10.1002/mc.23839","DOIUrl":"10.1002/mc.23839","url":null,"abstract":"Never in mitosis gene A (NIMA)-related kinase 2 (NEK2) is a crucial serine-threonine kinase involved in the process of cell mitosis. However, the precise relationship between NEK2 and esophageal squamous cell carcinoma (ESCC) remains inadequately understood. NEK2 expression in ESCC tissues was assessed through bioinformatics analysis, reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemistry, revealing a correlation with ESCC patient prognosis. Cultured ESCC cells and human normal esophageal epithelial cells (HEEC) were used to investigate the effects of NEK2 knockdown on the development and progression of ESCC by integrated confluence algorithm, colony formation, wound-healing, transwell, and ESCC xenograft tumor model, in vitro and in vivo. In ESCC tissues, NEK2 was found to be significantly upregulated, and its expression correlated with poor prognosis in ESCC patients. NEK2 may facilitate ESCC development by regulating cell proliferation, migration, and invasion. Additionally, results from in vivo experiments suggested that NEK2 knockdown can inhibit tumor growth. Moreover, forkhead box M1 (FOXM1) was identified as a potential downstream target of NEK2 in the regulation of ESCC, with its overexpression reversing the effects of NEK2 knockdown on ESCC. Mechanistic studies also indicated that NEK2 may promote the malignant progression of ESCC by inhibiting cellular senescence through the activation of the FOXM1/c-Myc/p27 signaling pathways, which may provide a novel perspective for the management of ESCC.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"244-259"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 a Novel RUNX1::STX2 Fusion in Mixed-Phenotype Acute Leukemia (MPAL) With BCR::ABL1. 在伴有 BCR::ABL1 的混合表型急性白血病 (MPAL) 中发现新型 RUNX1::STX2 融合体

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-02-01 Epub Date: 2024-11-27 DOI: 10.1002/mc.23850

Yuan Long, Qi Xu, Jing Li, Bei-Cai Liu, Peng Cheng, Jun Luo, Shengbin Zhao, Ping Chen, Zhen-Fang Liu

引用次数: 0

RETRACTION: Glyoxalase 2 Drives Tumorigenesis in Human Prostate Cells in a Mechanism Involving Androgen Receptor and p53-p21 Axis. 回归：糖醛酸酶 2 在涉及雄激素受体和 p53-p21 轴的机制中驱动人类前列腺细胞的肿瘤发生。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-02-01 Epub Date: 2024-11-15 DOI: 10.1002/mc.23849

{"title":"RETRACTION: Glyoxalase 2 Drives Tumorigenesis in Human Prostate Cells in a Mechanism Involving Androgen Receptor and p53-p21 Axis.","authors":"","doi":"10.1002/mc.23849","DOIUrl":"10.1002/mc.23849","url":null,"abstract":"Retraction: C. Antognelli, I. Ferri, G. Bellezza, P. Siccu, H. D. Love, V. N. Talesa, A. Sidoni, \"Glyoxalase 2 Drives Tumorigenesis in Human Prostate Cells in a Mechanism Involving Androgen Receptor and p53-p21 Axis,\" Molecular Carcinogenesis 56, no. 9 (2017): 2112-2126. https://doi.org/10.1002/mc.22668. The above article, published online on 04 May 2017, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by Wiley Periodicals LLC. The publisher received a report from a third party which detailed duplications of the cell staining images in Figures 2 F and 5 C of this article from a previously-published article by a different group of authors (Liu et al. 2015 [https://doi.org/10.3390/ijms160921897]). Additional investigation by the publisher uncovered duplications and rotations of cell staining images in Figures 2 F, 3B, and 5 C. The authors responded to an inquiry by the publisher, but they were not able to provide original, unmodified data or images for the experiments reported in their article. The authors were also not able to provide an explanation for the duplication of images with another article or the duplication and rotation of images within this article. The retraction has been agreed to because the duplication of images from another article which reports on different experimental conditions, as well as duplication and rotation of images between figures in this article, fundamentally compromises the conclusions of the article. The authors did not respond to our notice regarding the retraction.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"377"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

CD137 Protein Expression Pattern Determines the Functional Role of Galectin-9 in Colorectal Cancer. CD137蛋白表达模式决定了Galectin-9在结直肠癌中的功能作用

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-02-01 Epub Date: 2024-11-06 DOI: 10.1002/mc.23838

Yongping Huang, Xue Huang, Zhengming Zhu, Wubulikasimu Wulamu, Kai Huang, Dejun Tang, Jinlong Yu

{"title":"CD137 Protein Expression Pattern Determines the Functional Role of Galectin-9 in Colorectal Cancer.","authors":"Yongping Huang, Xue Huang, Zhengming Zhu, Wubulikasimu Wulamu, Kai Huang, Dejun Tang, Jinlong Yu","doi":"10.1002/mc.23838","DOIUrl":"10.1002/mc.23838","url":null,"abstract":"The rapid advancement of single-cell sequencing technology has generated extensive data, providing critical resources for colorectal cancer (CRC) research. This study conducts a detailed analysis of CRC single-cell sequencing data to develop a novel clinical prognostic tool and explore potential therapeutic targets for the LGALS9 gene. Using the Scissor algorithm, we created a CRC prognostic scoring system (SDRS) based on 13 key genes, with particular focus on LGALS9 and its protein, Galectin-9, in mice CRC model with altered CD137 expression. Our findings demonstrate that the SDRS accurately reflects clinical and pathological features of CRC patients, acting as an independent predictor of outcomes. LGALS9 expression is generally reduced in CRC tissues and is associated with poorer prognosis. We also observed a strong positive correlation between LGALS9 and CD137 expression, with CD137 showing significant variability in CRC tissues. In mouse models with CD137 overexpression, Galectin-9 treatment led to notable antitumor effects and increased infiltration of activated T cells. In contrast, in CD137-deficient models, Galectin-9 promoted tumor growth with limited T cell presence. These results suggest that the role of LGALS9 in CRC may depend on CD137 expression, highlighting the potential of LGALS9 as a therapeutic target. CD137 levels may serve as a key indicator for predicting the effectiveness of this treatment strategy.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"226-243"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Molecular Analysis of Genes CEBPA, NPM1, IDH1, and RUNX1 Polymorphisms as Biomarker Potential in Leukemia Patients. 作为白血病患者潜在生物标记物的 CEBPA、NPM1、IDH1 和 RUNX1 基因多态性的分子分析

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-02-01 Epub Date: 2024-11-20 DOI: 10.1002/mc.23846

Kashif Bashir, Sadia Abdul Ghafar, Afifa Tur Rehman, Tayyaba Waris, Fatima Farooq, Amin A Alamin

{"title":"Molecular Analysis of Genes CEBPA, NPM1, IDH1, and RUNX1 Polymorphisms as Biomarker Potential in Leukemia Patients.","authors":"Kashif Bashir, Sadia Abdul Ghafar, Afifa Tur Rehman, Tayyaba Waris, Fatima Farooq, Amin A Alamin","doi":"10.1002/mc.23846","DOIUrl":"10.1002/mc.23846","url":null,"abstract":"Leukemia is found in approximately 2.3 million people worldwide and causes many deaths all over the world. This research study was conducted to figure out the link of single nucleotide polymorphisms of genes CEBPA (rs34529039), NPM1 (rs753788683), IDH1 (of rs11554137) and RUNX1 (rs13051066) polymorphisms as biomarker potential in leukemia patients. A total of 600 subjects were included in the study which included 300 patients and 300 healthy controls with age and gender matched. After DNA extraction, PCR was carried out to analyze polymorphisms of selected genes. A significant association with increased risk of leukemia by almost twofolds is observed in homozygous mutant (AA) of rs34529039 SNP of gene CEBPA (odds ratio [OR] = 1.71; 95% confidence interval [CI] = 1.04-2.82; p = 0.03) while highly significant association but with decrease risk of leukemia is observed in heterozygote genotype (CA) of same SNP (OR = 0.36; 95% CI = 0.22-0.59; p = 0.0001). A highly significant association with increased risk of leukemia up to twofolds is observed in heterozygote genotype (AG) of rs753788683 of gene NPM1 (OR 2.10: 95% CI 1.32-3.36 p = 0.0017) while increasing risk by two-fold and show significant association in homozygous mutant (AA) (OR = 1.75; 95% Cl = 1.09-2.79; p = 0.01). Leukemia risk increases by twofold and shows significant association in the homozygous mutant (AA) of rs11554137 (OR = 1.75; 95%Cl = 1.09-2.79; p = 0.01). Leukemia risk increases by twofold and shows significant association in the homozygous mutant (AA) of rs13051066 of gene RUNX1 (OR = 0.63; 95%Cl = 0.39-1.63; p = 0.06).","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"357-368"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Clinical and Genomic Phenotype of Brain Metastasis in Nasopharyngeal Carcinoma. 鼻咽癌脑转移的临床和基因组表型

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-02-01 Epub Date: 2024-11-22 DOI: 10.1002/mc.23853

Ying-Peng Peng, Shuai Yang, Jianzhong He, Qiaodan Liu, Xuanzi Li, Fan-Gen Kong, Si-Yang Wang, Ye Liu

{"title":"Clinical and Genomic Phenotype of Brain Metastasis in Nasopharyngeal Carcinoma.","authors":"Ying-Peng Peng, Shuai Yang, Jianzhong He, Qiaodan Liu, Xuanzi Li, Fan-Gen Kong, Si-Yang Wang, Ye Liu","doi":"10.1002/mc.23853","DOIUrl":"10.1002/mc.23853","url":null,"abstract":"Brain metastasis in nasopharyngeal carcinoma is a rare but poor prognosis clinical problem. This study aims to investigate the clinical characteristics and identify the genomic profiling of nasopharyngeal carcinoma brain metastasis. Patients with a diagnosis of nasopharyngeal carcinoma who visited at the Fifth Affiliated Hospital of Sun Yat-sen University since January 2013 to December 2023 were retrospectively collected. Clinical data of patients diagnosed with nasopharyngeal carcinoma brain metastasis were extracted. Paraffin blocks of NPC brain metastases were acquired for immunohistochemistry and genetic testing. High-throughput second generation sequencing was performed for genomic analysis. The mutation landscape was further analyzed. Of the 2378 NPC patients from our database, only six were clinically diagnosed with nasopharyngeal carcinoma brain metastasis. Three were pathologically diagnosed with nasopharyngeal carcinoma brain metastasis. The time interval from the first diagnosis of nasopharyngeal carcinoma to brain metastasis was 15-56 months. The common sites of brain metastasis were frontal lobe and cerebellum, and could be single or multiple, cystic or solid lesions. The OS ranged from 7 to 48 months. Single nucleotide variants were found in 32 genes, such as PTEN, TP53, NFKBIA, KMT2C, and NOTCH1. Copy number variation occurred in five genes, including PTEN, CCDN1, FGF19, FGF3 and FGF4. PTEN and fibroblast growth factors might be involved in the molecular regulation of brain metastasis in nasopharyngeal carcinoma.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"369-376"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

The Mechanism of TRIM21 Inhibiting the Invasion and Migration of ccRCC by Stabilizing ASS1. TRIM21 通过稳定 ASS1 抑制 ccRCC 侵袭和迁移的机制

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-02-01 Epub Date: 2024-11-08 DOI: 10.1002/mc.23840

Zhe Yang, Jihao Cai, Jingjing Li, Xiangjie Liu, Wenjing Liu, Kun Cui, Ziyuan Bai, Yurong Dong, Dongmei Peng, Qiuxin Duan, Asif Shahzad, Qiao Zhang

{"title":"The Mechanism of TRIM21 Inhibiting the Invasion and Migration of ccRCC by Stabilizing ASS1.","authors":"Zhe Yang, Jihao Cai, Jingjing Li, Xiangjie Liu, Wenjing Liu, Kun Cui, Ziyuan Bai, Yurong Dong, Dongmei Peng, Qiuxin Duan, Asif Shahzad, Qiao Zhang","doi":"10.1002/mc.23840","DOIUrl":"10.1002/mc.23840","url":null,"abstract":"Clear cell renal cell carcinoma (ccRCC) is characterized by its aggressive invasion and metastasis, presenting significant clinical challenges. Gaining insights into the molecular mechanisms underlying its progression is crucial for the development of effective therapeutic strategies. Addressing a critical knowledge gap in understanding ccRCC tumorigenesis, this study aims to elucidate the expression patterns of TRIM21 in ccRCC, unravel its impact on ccRCC patient prognosis, and investigate the regulatory role of TRIM21 in ASS1 expression and urea cycle dysregulation within the context of ccRCC. The results demonstrate that TRIM21 is downregulated in ccRCC, and low expression of TRIM21 predicts an unfavorable prognosis for ccRCC patients. Furthermore, the upregulation of TRIM21 can inhibit the migration and invasion of ccRCC cells by regulating the ubiquitination modification of ASS1. This not only expands the functional role of TRIM21 in ccRCC tumorigenesis but also demonstrates its ability to reverse urea cycle dysregulation through stabilizing ASS1 expression. Specifically, abnormal downregulation of TRIM21 in ccRCC reduces K63 ubiquitination modification of ASS1, leading to decreased stability of the ASS1 protein, aggravated urea cycle dysregulation, and facilitated migration and invasion of ccRCC cells. Additionally, reduction in ASS1 reverses the depressed migration and invasion caused by overexpression of TRIM21 in ccRCC cells. In summary, our findings contribute to a deeper understanding of the functional role played by TRIM21 in ccRCC progression, pinpoint a unique and novel regulatory mechanism involving ectopic downregulation-mediated ASS1 ubiquitination modification and urea cycle dysfunction during ccRCC progression, and provide fresh insights for further investigation into the pathogenesis and metabolic reprogramming associated with ccRCC.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"260-278"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Zinc Finger Protein 263 Augments Autophagy and Promotes Intrahepatic Cholangiocarcinoma Proliferation. 锌指蛋白 263 可增强自噬作用并促进肝内胆管癌增殖

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-02-01 Epub Date: 2024-11-18 DOI: 10.1002/mc.23847

Zaihua Yan, Yadan Du, Yawen Chen, Jian Yang, Haoyang Zhang, Mingxu Da

{"title":"Zinc Finger Protein 263 Augments Autophagy and Promotes Intrahepatic Cholangiocarcinoma Proliferation.","authors":"Zaihua Yan, Yadan Du, Yawen Chen, Jian Yang, Haoyang Zhang, Mingxu Da","doi":"10.1002/mc.23847","DOIUrl":"10.1002/mc.23847","url":null,"abstract":"Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer characterized by a poor prognosis. Despite Zinc finger proteins (ZNFs) importance in tumor development and progression, it is unknown how dysregulated ZNF263 contributes to intrahepatic cholangiocarcinoma. This study aimed to determine whether ZNF263 plays an oncogenic role in ICC progression. The microarray of tumor tissues from clinical intrahepatic cholangiocarcinoma was immunohistochemically analyzed for ZNF263. Based on plate colony formation, CCK8, and tumor xenograft models, ZNF263 was assessed for its biological function. Mechanistically, CUT&Tag, RNA-seq, CHIP-PCR, Dual luciferase reporter assay, Western blotting, transmission electron microscopy (TEM), and immunohistochemical staining were employed. ZNF263 expression was elevated in intrahepatic cholangiocarcinoma tissues compared to nontumor tissues, which negatively impacted patient outcomes. Notably, ZNF263 overexpression promoted ICC cells proliferation via enhancing autophagy, whereas ZNF263 knockdown inhibited ICC cells proliferation. Furthermore, ZNF263 binds to the enhancer region of ULK1 and mediates its expression. ULK1 over-expressing ameliorated ZNF263 knockdown-induced inhibition of CRC proliferation. By activating the ULK1-autophagy axis, ZNF263 promotes proliferation of ICC and is potentially a prognostic or therapeutic target of ICC.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"317-328"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Imatinib Impedes EMT and Notch Signalling by Inhibiting p300 Acetyltransferase in Breast Cancer Cells. 伊马替尼通过抑制乳腺癌细胞中的 p300 乙酰转移酶阻碍 EMT 和 Notch 信号传导

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-02-01 Epub Date: 2024-11-19 DOI: 10.1002/mc.23848

Shilpi Sarkar, Thirukumaran Kandasamy, Siddhartha Sankar Ghosh

{"title":"Imatinib Impedes EMT and Notch Signalling by Inhibiting p300 Acetyltransferase in Breast Cancer Cells.","authors":"Shilpi Sarkar, Thirukumaran Kandasamy, Siddhartha Sankar Ghosh","doi":"10.1002/mc.23848","DOIUrl":"10.1002/mc.23848","url":null,"abstract":"Breast cancer remains a leading cause of cancer-related mortality among women, with current therapeutic approaches often limited by resistance and recurrence, especially in aggressive subtypes like triple-negative breast cancer. Drug repurposing has emerged as a promising strategy to address these challenges. In this study, we investigate the potential of Imatinib, a repurposed tyrosine kinase inhibitor, to inhibit epithelial-mesenchymal transition (EMT) in breast cancer cells by modulating the Notch signalling pathway. Our findings reveal that Imatinib treatment leads to a significant reduction in cancer cell stemness, invasiveness, and migration potential, alongside decreased colony-forming ability. EMT reversal was marked by a 2.71-fold increase in E-cadherin expression, with concurrent downregulation of mesenchymal markers, including Fibronectin (1.78-fold) and Slug (2.15-fold). Mechanistically, Imatinib was found to inhibit p300 acetyltransferase activity, resulting in reduced levels of H3K18Ac and H3K27Ac, which in turn led to the downregulation of key Notch pathway proteins such as HES1 (2.94-fold), AKT (2.08-fold), and p21 (1.88-fold). These results highlight the ability of Imatinib to suppress EMT through modulation of the Notch signalling pathway, offering a novel therapeutic avenue for breast cancer treatment. Overall, Imatinib demonstrates considerable potential for repurposing in breast cancer management by targeting critical oncogenic pathways involved in EMT and cancer progression.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"344-356"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

The Role of SMAD7 in the Epigenetic Regulation of TGF-β Targets in the Metastasis of Ovarian Cancer. SMAD7 在卵巢癌转移过程中对 TGF-β 靶点的表观遗传调控中的作用

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-02-01 Epub Date: 2024-11-14 DOI: 10.1002/mc.23843

Lin-Yu Chen, Shu-Yi Yang, Jian-Liang Chou, Han-Lin Chou, Chia-Chou Yeh, Chien-Chih Chiu, Hung-Cheng Lai, Michael W Y Chan, Jing-Siang Jhang

{"title":"The Role of SMAD7 in the Epigenetic Regulation of TGF-β Targets in the Metastasis of Ovarian Cancer.","authors":"Lin-Yu Chen, Shu-Yi Yang, Jian-Liang Chou, Han-Lin Chou, Chia-Chou Yeh, Chien-Chih Chiu, Hung-Cheng Lai, Michael W Y Chan, Jing-Siang Jhang","doi":"10.1002/mc.23843","DOIUrl":"10.1002/mc.23843","url":null,"abstract":"The role of TGF-β signaling in the epigenetic modifications involved in ovarian cancer is not fully understood. This study investigated the relationship between TGF-β signaling, epigenetic modifications, and cellular behaviors in ovarian cancer. We found that E-cadherin, a key cell adhesion molecule, underwent epigenetic silencing via promoter DNA hypermethylation in ovarian cancer cell lines and that this was accompanied by the upregulation of vimentin, which is indicative of a mesenchymal and invasive phenotype. DNA-demethylating agents restored E-cadherin expression, which suggests that TGF-β signaling mediates this epigenetic silencing. Overexpression of SMAD7, an inhibitory component of TGF-β signaling, reversed E-cadherin silencing, which suggests a role of SMAD7 in modulating the epigenetic status. Functionally, SMAD7 overexpression inhibited the migration and invasion in ovarian cancer cells, which suggests its therapeutic potential for suppressing metastasis. Clinically, ovarian cancer patients with high SMAD7 expression had significantly longer disease-free survival. Mechanistically, SMAD7 overexpression decreased the acetylation of H3K9 and the binding of the transcriptional repressor TWIST1 at the E-cadherin promoter, which promoted its demethylation and reactivation. Disruption of TGF-β signaling upregulated SMAD4 target genes, which are silenced by epigenetic mechanisms, a finding that suggests broader therapeutic implications. Overall, our results provide insights into the role of TGF-β-mediated epigenetic regulation in ovarian cancer metastasis and underscore the therapeutic potential of targeting TGF-β signaling and its downstream effectors. Further research is needed to elucidate the underlying mechanisms and validate these therapeutic strategies.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"290-304"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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