Molecular Carcinogenesis最新文献

B4GALT3 as a Key Glycosyltransferase Gene in Multiple Myeloma Progression: Insights From Bioinformatics, Machine Learning, and Experimental Validation. B4GALT3是多发性骨髓瘤进展中的关键糖基转移酶基因：来自生物信息学、机器学习和实验验证的见解。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-13 DOI: 10.1002/mc.70013

Apeng Yang, Mengying Ke, Lin Feng, Ye Yang, Junmin Chen, Zhiyong Zeng

{"title":"B4GALT3 as a Key Glycosyltransferase Gene in Multiple Myeloma Progression: Insights From Bioinformatics, Machine Learning, and Experimental Validation.","authors":"Apeng Yang, Mengying Ke, Lin Feng, Ye Yang, Junmin Chen, Zhiyong Zeng","doi":"10.1002/mc.70013","DOIUrl":"https://doi.org/10.1002/mc.70013","url":null,"abstract":"Glycosylation abnormalities are critical in the progression of various cancers. However, their role in the onset and prognosis of multiple myeloma (MM) remains underexplored. This study aims to identify glycosyltransferase (GT)-related biomarkers and investigate their underlying mechanisms in MM. GT-related genes were extracted from the MMRF-CoMMpass and GSE57317 data sets. Potential biomarkers were identified using Cox regression and Lasso analyses. A glycosyltransferase-related prognostic model (GTPM) was developed by evaluating 113 machine learning algorithm combinations. The expression of B4GALT3, a key gene identified through this model, was analyzed in MM bone marrow samples using immunohistochemistry, quantitative PCR, and Western blot. Functional roles of B4GALT3 in MM cell behavior were assessed through knockdown experiments, and its mechanism of action was investigated. The GTPM stratified MM patients into high- and low-risk groups, with significantly better survival in the low-risk group (HR = 55.94, 95% CI = 40.48-77.31, p < 0.001). The model achieved AUC values of 0.98 and 0.99 for 1- and 3-year overall survival, outperforming existing gene signatures (including EMC92, UAMS70, and UAMS17). B4GALT3 expression was significantly elevated in advanced MM stages (p < 0.001) and correlated with poorer survival. Knockdown of B4GALT3 reduced MM cell proliferation, invasion, and increased apoptosis. Mechanistic analyses revealed that B4GALT3 modulates MM cell behavior via the Wnt/β-catenin/GRP78 pathway, primarily by regulating endoplasmic reticulum (ER) stress. This study developed a novel GTPM for predicting survival in MM and identified B4GALT3 as a key gene influencing disease progression. Experimental evidence highlights B4GALT3's role in modulating ER stress and Wnt/β-catenin pathways, positioning it as a potential prognostic biomarker and therapeutic target in MM.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626747","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

Osteoglycin Inhibits the Progression of Lung Adenocarcinoma by Modulating ICAM1-Mediated Cell Adhesion via the PI3K/AKT Pathway. 骨苷通过PI3K/AKT通路调节icam1介导的细胞粘附抑制肺腺癌的进展

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-13 DOI: 10.1002/mc.70007

Shangwei Xu, Chunji Chen, Hongwei Liu, Shuai Jiang, Zheng Li, Yun Wu

引用次数: 0

Combined Inhibition of XPO1 and DNA Methylation Exerts Synergistic Effects in DLBCL. XPO1和DNA甲基化联合抑制在DLBCL中发挥协同作用。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-13 DOI: 10.1002/mc.70014

Qi Li, Xiaofeng Xue, Si Chen, Xinyun Zhang, Yuchen Zhang, Ruijing Hu, Xinyuan Zhang, Linlin Qin, Menglu Chen, Wenzhuo Zhuang, Bingzong Li

{"title":"Combined Inhibition of XPO1 and DNA Methylation Exerts Synergistic Effects in DLBCL.","authors":"Qi Li, Xiaofeng Xue, Si Chen, Xinyun Zhang, Yuchen Zhang, Ruijing Hu, Xinyuan Zhang, Linlin Qin, Menglu Chen, Wenzhuo Zhuang, Bingzong Li","doi":"10.1002/mc.70014","DOIUrl":"https://doi.org/10.1002/mc.70014","url":null,"abstract":"Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma characterized by high rates of relapse and limited responsiveness to standard chemotherapy. Selinxor, a selective inhibitor of XPO1, exhibited antitumor activity in various cancers. However, clinical trial results revealed that selinexor monotherapy exhibited unsatisfactory efficacy in DLBCL. Our study indicated that XPO1 expression was increased in DLBCL and was correlated with poor outcomes of DLBCL patients. Comprehensive proteomic and transcriptomics analysis showed that selinexor has significant impacts on various biological processes in DLBCL. Furthermore, we explored combination strategies involving selinexor to enhance DLBCL treatment. We examined the combined effects of selinexor with decitabine (DAC) and lenalidomide (LEN), and found that selinexor exhibited a synergistic effect with DAC against DLBCL. Further analysis revealed that DAC exerted a synergistic antitumor effect with selinexor by reversing the DNMT1 expression and DNA methylation alterations induced by selinexor. Overall, these findings provided valuable insights into the global impact of selinexor on DLBCL. The combination therapy of selinexor and DAC emerges as a highly promising strategy for effectively treating DLBCL, holding great potential for clinical application.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626748","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 Plasma rRNA-Derived Small RNA Biomarkers for Diagnosis of Colorectal Cancer. 血浆rrna来源的小RNA生物标志物在结直肠癌诊断中的鉴定

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-13 DOI: 10.1002/mc.70012

Xinliang Gu, Danping Zhu, Youyue Li, Xinwei Liu, Xincheng Yang, Junjie Nie, Tao Xu, Huiling Sun, Bin Zhu, Yuqin Pan, Shukui Wang

{"title":"Identification of Plasma rRNA-Derived Small RNA Biomarkers for Diagnosis of Colorectal Cancer.","authors":"Xinliang Gu, Danping Zhu, Youyue Li, Xinwei Liu, Xincheng Yang, Junjie Nie, Tao Xu, Huiling Sun, Bin Zhu, Yuqin Pan, Shukui Wang","doi":"10.1002/mc.70012","DOIUrl":"https://doi.org/10.1002/mc.70012","url":null,"abstract":"Colorectal cancer (CRC) ranks among the most aggressive malignancies globally, with advanced-stage patients exhibiting notably low survival rates. Consequently, there is an urgent imperative to identify novel biomarkers characterized by high sensitivity and specificity. Ribosomal RNA-derived small RNAs (rsRNAs), which originate from ribosomal RNAs, represent the most prevalent small noncoding RNAs (sncRNAs) in CRC tissues and plasma. Thus, the development of a diagnostic panel comprising multiple rsRNAs holds considerable significance for CRC diagnosis. Utilizing PANDORA-seq, we have, for the first time, delineated a novel sncRNA expression profile in CRC tissues and plasma, identifying rsRNAs as the predominant sncRNAs within these contexts. We identified six rsRNAs that were significantly upregulated in CRC plasma and subsequently constructed a co-diagnostic panel. This panel demonstrated an area under the curve (AUC) value of 0.898, which increased to 0.942 when combined with clinically utilized tumor markers, indicating robust diagnostic efficacy. Our study is the first to establish that rsRNAs are the most abundantly expressed sncRNAs in CRC tissues and plasma. We have developed an rsRNA panel with substantial diagnostic efficacy in CRC plasma, presenting promising potential as diagnostic biomarkers.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626749","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

Overexpression of Aquaporin-1 Promotes Epithelial-Mesenchymal Transition and Cancer Stem Cell Properties via Wnt/β-Catenin Signaling Pathway in Advanced Breast Cancer Cells. 水通道蛋白-1的过表达通过Wnt/β-Catenin信号通路促进晚期乳腺癌细胞上皮-间质转化和癌症干细胞特性

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-09 DOI: 10.1002/mc.70009

Shan Wu, Haiyan Hu, Xiuhong Wang, Zhan Hua, Jianjun Zhou

{"title":"Overexpression of Aquaporin-1 Promotes Epithelial-Mesenchymal Transition and Cancer Stem Cell Properties via Wnt/β-Catenin Signaling Pathway in Advanced Breast Cancer Cells.","authors":"Shan Wu, Haiyan Hu, Xiuhong Wang, Zhan Hua, Jianjun Zhou","doi":"10.1002/mc.70009","DOIUrl":"https://doi.org/10.1002/mc.70009","url":null,"abstract":"Tumor metastasis and the persistence of cancer stem cells (CSCs) are the main factors contributing to tumor malignancy, particularly in breast cancer. Uncovering the critical molecular mechanisms and therapeutic targets is essential for addressing this challenge. The present study revealed that aquaporin-1 (AQP1) was highly expressed in breast cancer and was closely associated with poor patient prognosis. AQP1 overexpression significantly enhanced multiple cellular processes in breast cancer cells, including cell proliferation, migration, invasion, spheroid formation, and three-dimensional (3D) spheroid invasion. Moreover, AQP1 activated the Wnt/β-catenin signaling pathway, and promoted the expression of epithelial-mesenchymal transition (EMT)-related markers (N-cadherin and vimentin) and CSC markers (SOX2 and c-Myc). Furthermore, small hairpin (sh)RNA-mediated downregulation of β-catenin confirmed the mechanism by which AQP1 promoted EMT and CSC properties through the activation of the Wnt/β-catenin signaling pathway. In conclusion, the present study elucidated the molecular mechanism through which AQP1 advanced breast cancer progression via the Wnt/β-catenin signaling pathway, providing insights into the mechanisms underlying breast cancer progression and offering valuable implications for developing novel therapeutic strategies.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591829","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

A-to-I RNA Edited miR-3167 Restrains Malignant Behaviors of Lung Adenocarcinoma by Influencing SSR2-Meditated Hippo Signaling. A-to-I RNA编辑的miR-3167通过影响ssr2介导的河马信号传导抑制肺腺癌的恶性行为

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-09 DOI: 10.1002/mc.70011

Dawei Qian, Dongsheng Zha, Yuanyao Sang, Jiangquan Tao, Bufeng Zhuang, Youshuang Cheng

{"title":"A-to-I RNA Edited miR-3167 Restrains Malignant Behaviors of Lung Adenocarcinoma by Influencing SSR2-Meditated Hippo Signaling.","authors":"Dawei Qian, Dongsheng Zha, Yuanyao Sang, Jiangquan Tao, Bufeng Zhuang, Youshuang Cheng","doi":"10.1002/mc.70011","DOIUrl":"https://doi.org/10.1002/mc.70011","url":null,"abstract":"Recently, RNA editing, as a natural modification process of RNA molecules, has aroused extensive interest in the scientific community. This study elaborated the role and process of A-to-I RNA edited miR-3167 in lung adenocarcinoma (LUAD). RT-qPCR and Western blot analysis were employed for the detection of miRNA and gene expressions. The function of miRNA was investigated through Transwell, CCK-8 and flow cytometry assays. Dual-luciferase reporter assay was conducted to assess the link between gene and miRNA. The level of A-to-I RNA editing for miR-3167 was declined in LUAD tissues, which was linked to adverse clinical outcomes and prognosis in LUAD patients. In LUAD, ADAR2 enzyme is responsible for mediating the A-to-I RNA editing of miR-3167. Functionally, LUAD cell viability and metastasis were scarcely influenced by wt-miR-3167, while miR-3167 displayed antitumor activity in LUAD post A-to-I RNA editing. Mechanically, SSR2 is directly targeted by ed-miR-3167 in LUAD, but not wt-miR-3167. SSR2 served as a tumor promoter in LUAD progression by inactivating Hippo signaling and hindering immune infiltration. Ed-miR-3167 exerted tumor inhibitory effect in LUAD by weakening the carcinogenesis of SSR2. A-to-I RNA edited miR-3167 curbs malignant behaviors of LUAD by activating Hippo signaling through downregulating SSR2, indicating that edited miR-3167 has the potential as a therapeutic target for LUAD.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591828","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

MAZ Coordinates With HDAC1 to Promote Hepatocarcinoma Proliferation and Metastasis Through Transcriptional Repression of CSK. MAZ与HDAC1协同通过抑制CSK转录促进肝癌增殖和转移

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-06 DOI: 10.1002/mc.70005

Rongfang Qiu, Weiqian Chen, Siyu Zhao, Haixia Zhao, Tian Qiu, Qin Hu, Ziwei Xu, Lulu Zeng, Chunli Kong, Cong Zhang, Qiaoyou Weng, Aiqi Zhao, Jiaoli Wang, Yanyu He, Jianfei Tu, Minjiang Chen, Zhongwei Zhao, Yang Yang, Jiansong Ji

{"title":"MAZ Coordinates With HDAC1 to Promote Hepatocarcinoma Proliferation and Metastasis Through Transcriptional Repression of CSK.","authors":"Rongfang Qiu, Weiqian Chen, Siyu Zhao, Haixia Zhao, Tian Qiu, Qin Hu, Ziwei Xu, Lulu Zeng, Chunli Kong, Cong Zhang, Qiaoyou Weng, Aiqi Zhao, Jiaoli Wang, Yanyu He, Jianfei Tu, Minjiang Chen, Zhongwei Zhao, Yang Yang, Jiansong Ji","doi":"10.1002/mc.70005","DOIUrl":"https://doi.org/10.1002/mc.70005","url":null,"abstract":"The transcription factor Myc-associated zinc finger protein (MAZ) is highly expressed in various malignant tumors, and it is known to activate the expression of a large number of proto-oncogenes through transcription. However, the specific molecular mechanism of how MAZ regulates transcriptional repression in hepatocarcinoma remains unclear. To identify the interacting proteins of MAZ, we employed immunoaffinity purification followed by silver-stain mass spectrometry. RNA-seq analysis, RT-PCR, and ChIP assays were utilized to examine the target genes and signaling pathways coregulated by MAZ and HDAC1. Additionally, we conducted EdU incorporation, colony formation, growth curve, TUNEL, transwell, and wound-healing assays, along with immunohistochemical staining, in vivo tumor xenografts, and bioluminescence metastasis assays, to explore the role of the MAZ/HDAC1 complex in tumorigenesis. Our findings revealed that MAZ binds to the transcriptional inhibitory complexes HDAC1, RBBP7, and CUL4B. Transcriptome analysis revealed that MAZ and HDAC1 cooperatively regulate the expression of the CSK gene. Knockdown of either MAZ or HDAC1 activates CSK expression, subsequently inhibiting the MAPK/ERK, STAT3, and PI3K/AKT signaling pathways, thereby suppressing the proliferation and metastasis of hepatocellular carcinoma cells. The proliferation and metastasis phenotypes induced by MAZ knockdown can be rescued by simultaneous knockdown of CSK. In vivo experiments have demonstrated that MAZ knockdown inhibits tumorigenesis and metastasis in mice. Our findings highlight a novel mechanism wherein MAZ plays a transcriptional inhibitory role by recruiting HDAC1 to catalyze histone deacetylation, and the MAZ/HDAC1 complex inhibits CSK expression, thus promoting tumor proliferation and metastasis.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575829","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

Nigericin Suppresses the Wnt/β-catenin Signaling in Pancreatic Cancer Through Targeting Pre-miR-374b-PRKCA/HBP1 Axis. 尼日利亚蛋白通过靶向Pre-miR-374b-PRKCA/HBP1轴抑制胰腺癌中Wnt/β-catenin信号传导

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-06 DOI: 10.1002/mc.70008

Fei Liu, Tianlong Tang, Yan Pan, Qiaoming Zhi, Ye Han, Zhihua Xu

{"title":"Nigericin Suppresses the Wnt/β-catenin Signaling in Pancreatic Cancer Through Targeting Pre-miR-374b-PRKCA/HBP1 Axis.","authors":"Fei Liu, Tianlong Tang, Yan Pan, Qiaoming Zhi, Ye Han, Zhihua Xu","doi":"10.1002/mc.70008","DOIUrl":"https://doi.org/10.1002/mc.70008","url":null,"abstract":"Our previous studies identified the differentially expressed coding and noncoding RNAs during the nigericin-mediated damage by the high-throughput RNA sequencing. However, these reports provided insights into nigericin only through the bioinformatics methods. The anticancer mechanisms of nigericin in pancreatic cancer (PC) have still not been elucidated. In this study, PC cells were exposed to increasing concentrations of nigericin at different time periods, and the corresponding 50% inhibiting concentration (IC50) values were calculated. Then the effects on the biological functions of PC cells were evaluated. Subsequent experiments, including the high-throughput RNA sequencing, qRT-PCR, western blot, TOP/FOP-Flash reporter, Co-Immunoprecipitation (Co-IP) and luciferase reporter assays were employed to reveal the mechanisms of nigericin. In addition, the inhibitory effects of nigericin on PC cells were accessed in the subcutaneous tumor and peritoneal disseminated models. The data showed that nigericin was extremely sensitive to PC cells, and influenced the abilities of cell proliferation, colony formation, apoptosis, migration and invasion. The results in vitro implied that nigericin suppressed the Wnt/β-catenin signaling by upregulating PRKCA and HBP1 mRNA expressions. Si-PRKCA, si-HBP1 or silencing these two molecules simultaneously could attenuate the inactivation of Wnt/β-catenin signaling induced by nigericin. Furthermore, the dual strands of pre-miR-374b were proved to down-regulate the expressions of PRKCA and HBP1 coordinately through their mature products miR-374b-5p and -3p. Overexpression of pre-miR-374b might partly antagonize the suppressing effects of nigericin in PC cells. Suppressing the Wnt/β-catenin signaling pathway by targeting pre-miR-374b-PRKCA/HBP1 axis might represent a novel mechanism of nigericin in PC. Nigericin remained a candidate of preclinical application for PC.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575830","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

Synergistic Inhibition of Prostate Cancer Progression in Mice With a Combination of Curcumin and Ursolic Acid in the Diet. 膳食中姜黄素和熊果酸联合对小鼠前列腺癌进展的协同抑制作用。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-06 DOI: 10.1002/mc.70000

Chelsea A Friedman, Achinto Saha, Rachel Clark, Carly Wilder, Jordan Wright, John DiGiovanni

{"title":"Synergistic Inhibition of Prostate Cancer Progression in Mice With a Combination of Curcumin and Ursolic Acid in the Diet.","authors":"Chelsea A Friedman, Achinto Saha, Rachel Clark, Carly Wilder, Jordan Wright, John DiGiovanni","doi":"10.1002/mc.70000","DOIUrl":"https://doi.org/10.1002/mc.70000","url":null,"abstract":"Prostate cancer (PCa) is the second leading cause of cancer-related death among American men, and its long latency offers a window for chemopreventive strategies. Phytochemicals, with their diverse impacts on cancer cell growth and metabolism, represent promising candidates for such strategies. Combining compounds like curcumin (Curc) and ursolic acid (UA), which target multiple pathways, can be advantageous in slowing tumor progression. Previous studies revealed the synergistic effects of Curc + UA in reducing tumor growth in a PCa allograft model. In this study, diet-based interventions were evaluated using two transgenic mouse models of PCa. Mice fed a Curc + UA-enriched diet exhibited significant inhibition of prostate tumor progression compared to single-agent diets in both HiMyc and PTEN knockout mouse models. Protein analyses of ventral prostate tissues from HiMyc mice indicated that the combination suppressed oncogenic signaling pathways, including STAT3, AKT, and mTORC1, while modulating cell regulatory proteins to inhibit tumor cell proliferation. Furthert mechanistic studies in mouse and human PCa cell lines confirmed that Curc + UA exerted pleiotropic effects by influencing oncogenic signaling, cell cycle regulation, mitochondrial function, unfolded protein response (UPR), and apoptosis, collectively contributing to its synergistic efficacy. These findings highlight the potential of Curc + UA to inhibit PCa progression through multitargeted mechanisms. The combination's superior efficacy over single agents underscores its promise as a chemopreventive or therapeutic strategy. This study provides a strong rationale for further mechanistic investigations and clinical development of Curc + UA for PCa prevention and treatment.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575831","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

Determine the Antimetastasis Effect of Artesunate in Lung Cancer-Driven Brain Metastasis Model. 确定青蒿琥酯在肺癌驱动脑转移模型中的抗转移作用。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-07-06 DOI: 10.1002/mc.70010

Minling Lu, Ting Wan, Qianling Huang, Jingjing Yao, Yaqiu Zheng, Shaofang Yu, Xiaomin Zhu, Xiaoyi Zeng, Zhongqiu Liu, Yuan Zheng, Linlin Lu

{"title":"Determine the Antimetastasis Effect of Artesunate in Lung Cancer-Driven Brain Metastasis Model.","authors":"Minling Lu, Ting Wan, Qianling Huang, Jingjing Yao, Yaqiu Zheng, Shaofang Yu, Xiaomin Zhu, Xiaoyi Zeng, Zhongqiu Liu, Yuan Zheng, Linlin Lu","doi":"10.1002/mc.70010","DOIUrl":"https://doi.org/10.1002/mc.70010","url":null,"abstract":"Brain metastasis (BM), most vital and common metastasis phenotype occurs during tumorigenesis, the incidence of which varied remarkedly in various cancers. Overwhelming evidence suggested blood-brain barrier (BBB) can attenuate the anti-BM efficacy of chemotherapies via hindering their penetration. This study aimed to investigate the preferential cancer type that is more prone to BM, and bioactive compound that suppress BM through penetrating BBB. By intracardiac injection of lung cancer cells, breast cancer cells and melanoma cells, BM models were established. By two cycles of primary-isolation and incubation of H446-luc cells to improve the incidence of BM. Artemisinin (ART) and its derivatives were evaluated to suppress BM in vitro and in vivo. Compared to lung cancer-driven BM (66.67%), the incidence of BM in breast cancer (16.67%-33.33%) and melanoma (33.33%) were extremely low. The incidence of BM in lung cancer increased from 66.67 (1st generation) to 80% (2nd generation). Compared to other ingredients, artesunate (ARTS) exerted a more significant inhibitory effect on cell proliferation, especially in lung cancer cells. Simultaneously, ARTS suppressed lung cancer migration via decreasing N-cadherin and Snail, and enhancing E-cadherin. Most importantly, we found that ARTS could strikingly suppress tumor growth in brain with high concentration, implying that ARTS might penetrate BBB and accumulate in brain tissue to hinder lung cancer-driven BM. Our findings not only suggest lung cancer exhibited tumor specificity in cancer-driven BM model, but also provide ARTS as a promising candidate for clinical treatment of lung cancer-relayed BM.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575828","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