Molecular Carcinogenesis最新文献_第3页

RETRACTION: Tumorigenic Study on Hepatocytes Coexpressing SV40 With Ras. 撤回：SV40与Ras共表达肝细胞的致瘤性研究。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-09-25 DOI: 10.1002/mc.70046

{"title":"RETRACTION: Tumorigenic Study on Hepatocytes Coexpressing SV40 With Ras.","authors":"","doi":"10.1002/mc.70046","DOIUrl":"https://doi.org/10.1002/mc.70046","url":null,"abstract":"Retraction: B. Sun, M. Chen, C. Hawks, P. J. Hornsby, and X. Wang, \"Tumorigenic Study on Hepatocytes Coexpressing SV40 With Ras,\" Molecular Carcinogenesis 45 no. 4 (2006): 213-219, https://doi.org/10.1002/mc.20137. The above article, published online on 19 September 2005 in Wiley Online Library (wileyonlinelibrary.com) has been retracted by agreement between the authors; the journal Editor-in-Chief; and Wiley Periodicals LLC. The authors identified a significant discrepancy between the legend of Figure 3 and its corresponding description in the Results section. Specifically, the figure legend cites the use of \"HCA2 cells,\" whereas the Results section explicitly describes experiments conducted with \"human hepatocyte lines HL-7702 and HL-7703.\" To resolve this discrepancy and validate the critical findings, the authors attempted to replicate the experiments using the original HL-7702/HL-7703 cell systems. However, two irremediable constraints precluded verification: First, the extended time interval of nearly two decades since publication had rendered the original biological materials nonviable due to natural degradation. Second, essential plasmid constructs required for experimental replication were permanently lost during multiple laboratory relocations over this period. Consequently, the core conclusions remain experimentally unverifiable. Given that the figure-result contradiction cannot be resolved through standard correction measures and considering the irretrievable inability to replicate the study's key outcomes, we conclude that the continued availability of this paper irreparably compromises the validity of the study's conclusions and risks perpetuating misleading information. Therefore, the article must be retracted.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138009","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

Inhibiting Cyclin-Dependent Kinase 13-Mediated Nuclear Ubiquitous Casein Kinase and Cyclin-Dependent Kinase Substrate 1 Phosphorylation Facilitates Oxidative Stress-Induced Apoptosis in Melanoma. 抑制周期蛋白依赖性激酶13介导的核泛在酪蛋白激酶和周期蛋白依赖性激酶底物1磷酸化促进氧化应激诱导的黑色素瘤细胞凋亡。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-09-25 DOI: 10.1002/mc.70040

Zhaohai Pan, Heng Ge, Pan Jiang, Dan Shi, Zihui Yang, Xin Zhang, Jie Huang, Chao Liang, Jun Lu, Qi Xie, Qiusheng Zheng, Defang Li

{"title":"Inhibiting Cyclin-Dependent Kinase 13-Mediated Nuclear Ubiquitous Casein Kinase and Cyclin-Dependent Kinase Substrate 1 Phosphorylation Facilitates Oxidative Stress-Induced Apoptosis in Melanoma.","authors":"Zhaohai Pan, Heng Ge, Pan Jiang, Dan Shi, Zihui Yang, Xin Zhang, Jie Huang, Chao Liang, Jun Lu, Qi Xie, Qiusheng Zheng, Defang Li","doi":"10.1002/mc.70040","DOIUrl":"https://doi.org/10.1002/mc.70040","url":null,"abstract":"Cellular responses after oxidative stress-induced deoxyribonucleic acid (DNA) damage (e.g., DNA double-strand break) control tumor cell proliferation, senescence, and apoptosis. The nuclear ubiquitous casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) ensures replication feasibility by modulating double-strand break repair necessary to regulate tumor cell proliferation. However, the regulatory mechanism of NUCKS1 in oxidative stress-induced melanoma cell apoptosis is not well characterized. In this study, we reported reduced phosphorylation of NUCKS1 during oxidative stress-mediated melanoma A375 and A875 cell apoptosis, and silencing of NUCKS1 obviously promoted A375 and A875 cell apoptosis. Mechanistically, cyclin-dependent kinase 13 (CDK13) was identified as a major upstream kinase to phosphorylate NUCKS1 and downregulated via ataxia telangiectasia mutated (ATM)/checkpoint kinase 2 (Chk2)/cell division cycle 25C (Cdc25C) axis during the process of oxidative stress-induced apoptosis. Moreover, we found that p-NUCKS1 could bind to tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein Zeta (YWHAZ) and subsequently regulate the level of BCL2-associated X (Bax), thereby leading to melanoma A375 and A875 cell apoptosis. Furthermore, we found that p-NUCKS1 was highly expressed in tumor specimens from melanoma patients, and silencing of NUCKS1 inhibited tumor growth in melanoma A375 and A875-bearing mouse models. Therefore, p-NUCKS1 could act as a potential target for melanoma treatment by mediating oxidative stress-induced apoptosis.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138056","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

SSR4 Promote Gastric Cancer Progression by Regulating Mitochondrial Oxidative Phosphorylation via NDUFB11 and ATP6AP1. SSR4通过NDUFB11和ATP6AP1调控线粒体氧化磷酸化促进胃癌进展。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-09-25 DOI: 10.1002/mc.70047

Aoshuang Li, Baixue Liao, Kaiwen Wu, Ruiling Fan, Binjun Zhu, Xiaobin Sun, Lei Liu

引用次数: 0

Novel Metabolic-Prognostic Integration Reveals TCF21-Mediated Mitochondrial Regulation in Endometrial Cancer. 新的代谢-预后整合揭示了tcf21介导的子宫内膜癌线粒体调控。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-09-22 DOI: 10.1002/mc.70041

Ciren Guo, Jianfeng Zheng, Xuefen Lin, Xiafei Ye, Xinyan Jiang, Yang Sun

{"title":"Novel Metabolic-Prognostic Integration Reveals TCF21-Mediated Mitochondrial Regulation in Endometrial Cancer.","authors":"Ciren Guo, Jianfeng Zheng, Xuefen Lin, Xiafei Ye, Xinyan Jiang, Yang Sun","doi":"10.1002/mc.70041","DOIUrl":"https://doi.org/10.1002/mc.70041","url":null,"abstract":"Despite endometrial cancer (EC) being a malignancy linked to metabolic disorders such as diabetes and obesity, its prognostic markers and metabolic dysregulation remain incompletely understood. Gene expression profiles and clinical data were obtained from TCGA. Metabolism-regulating genes (MRGs) were identified by intersecting genes linked to diabetes, obesity, and EC prognosis. A prognostic MRG-model was developed using LASSO Cox regression. Functional pathway features of the MRG-model were analyzed for prognostic signals, immune status, and antitumor therapy using methods such as gene set enrichment analysis, GSVA, ssGSEA, EPIC, CIBERSORT, and others. Machine learning algorithms identified the optimal MRG, TCF21, for in vivo and in vitro validation through experiments including colony formation, CCK8 assays, wound healing, Transwell assays, measurement of reactive oxygen species and ATP levels. We identified 72 candidate genes related to EC metabolism and progression. The MRG-model effectively distinguished high-risk from low-risk EC patients and demonstrated strong prognostic predictive capacity. Significant differences were observed between the two groups in clinical factors, functional pathways, immune characteristics, mutation profiles, and treatment recommendations. TCF21, with optimal performance, was selected for further study. TCF21 expression was significantly downregulated in EC and correlated with DNA methylation. As a tumor suppressor, TCF21 regulates proliferation, migration, invasion, and mitochondrial metabolism in EC via PDE2A. The MRG-model can serve as a robust tool for prognostic prediction and support personalized EC treatment, enhancing its clinical potential. TCF21 is methylated in EC, and its regulation of PDE2A governs the malignant phenotype and mitochondrial metabolism.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113881","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

Screening and Validation of Genes Associated With Lysosomal-Dependent Cell Death in Colorectal Cancer. 结直肠癌溶酶体依赖性细胞死亡相关基因的筛选和验证。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-09-18 DOI: 10.1002/mc.70024

Jianbin Zhuang, Chengquan Ma, Mingjian Yang, Weiliang Song

{"title":"Screening and Validation of Genes Associated With Lysosomal-Dependent Cell Death in Colorectal Cancer.","authors":"Jianbin Zhuang, Chengquan Ma, Mingjian Yang, Weiliang Song","doi":"10.1002/mc.70024","DOIUrl":"https://doi.org/10.1002/mc.70024","url":null,"abstract":"This study investigates the correlation between CRC and lysosomal-dependent cell death (LDCD) to identify potential therapeutic targets and prognostic indicators. Utilizing CRC datasets (TCGA-CRC) and GSE17538, differentially expressed genes and LDCD-related genes (LDCDRGs) were analyzed to identify candidate genes. A risk model was constructed using Cox regression analysis, proportional hazards test and least absolute shrinkage and selection operator analysis. Independent prognostic factors were determined through Cox analysis (univariate and multivariate). Additionally, nomogram establishment, enrichment analysis, tumor immune microenvironment analysis, sensitivity analysis of chemotherapeutic drugs and single-cell sequencing analysis were conducted. Furthermore, prognostic gene expression in CRC and normal groups was further evaluated in TCGA-CRC as well as in clinical samples. A total of 37 candidate genes were identified. ATP6V0A4, CLU and IL13RA2 were selected for constructing a risk model. The risk model, incorporating independent prognostic parameters such as risk score, age and pathological T stage, exhibited favorable diagnostic performance for CRC. Tumor immune microenvironment analysis showed higher dysfunction, exclusion, and tumor immune dysfunction and exclusion scores in the high-risk group compared to the low-risk group. Significant differences were observed in the 50% inhibitory concentration of 84 drugs between the two risk subgroups. ENCs and myeloid cells were regarded as key cells. Importantly, IL13RA2 exhibited higher expression in patients with CRC, while CLU was more highly expressed in normal samples. This study identified ATP6V0A4, CLU and IL13RA2 as potential biomarkers associated with lysosome-mediated cell death in CRC, providing insights for diagnosis and treatment.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081199","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

IGHA1 and IGHG1 Expression Panel Predicts Anti-PD-L1 Response in Muscle-Invasive Bladder Cancer. IGHA1和IGHG1表达预测肌肉浸润性膀胱癌抗pd - l1反应

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-09-08 DOI: 10.1002/mc.70033

Lin Zhou, Guopeng Yu, Zhongpeng Zheng, Bin Xu

{"title":"IGHA1 and IGHG1 Expression Panel Predicts Anti-PD-L1 Response in Muscle-Invasive Bladder Cancer.","authors":"Lin Zhou, Guopeng Yu, Zhongpeng Zheng, Bin Xu","doi":"10.1002/mc.70033","DOIUrl":"https://doi.org/10.1002/mc.70033","url":null,"abstract":"B cells located in tertiary lymphoid structures (TLSs) may undergo clonal expansion, somatic hypermutation, isotype switching, and tumor-specific antibody production, suggesting that antibody-producing plasma cells may be involved in antitumor immunity. This study used a combination of single-cell sequencing (five samples from our center, and four samples from PRJNA662018) and spatial transcriptome (one sample from our center, and four samples from GSE169379) research methods to investigate the relationship between TLSs and the immunoglobulin repertoire in muscle invasive bladder cancer (MIBC). 405 patients with MIBC from TCGA and 348 patients with metastatic urothelial carcinoma on PD-L1 inhibitor treatment from the IMvigor210 trial were included in this study. We identified IGHA1low IGHG1high patients could benefit more from cisplatin-based adjuvant chemotherapy and PD-L1 inhibitor. Further analyses revealed IGHA1low IGHG1high subgroup was linked to an antitumor immune microenvironment with highly immune effector cells. Spatial architecture unveils areas of B cell rich hot spots in TLS+ tumors. We found that some IGHG1 clonotypes appeared inside the TLS, and most IGHG1 clonotypes were distributed in the tumor bed after treatment. The diversity of the immunoglobulin repertoire, especially IGHG1 clonotype, was higher after treatment. IGHA1low IGHG1high patients was associated with antitumor immune microenvironment and the therapeutic response to adjuvant chemotherapy and PD-L1 inhibitor in MIBC. This study presents a spatial map of TLSs, where plasma cells of IGHG1 clonotypes mature within and disseminate around tumors. Plasma cells of IGHG1 clonotypes may cooperate with iCAF, macrophages and NK cells to kill tumor cells and improve the efficacy of immunotherapy.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015852","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

KIAA1429 and AlkB Homolog 5 Regulate Bladder Cancer Progression via N⁶-Methyladenosine-Dependent Modulation of Sonic Hedgehog Signaling. KIAA1429和AlkB同源物5通过n6 -甲基腺苷依赖的Sonic Hedgehog信号调节膀胱癌的进展。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-09-01 Epub Date: 2025-06-26 DOI: 10.1002/mc.70004

Zhimin Jiao, Xiaowu Liu, Xiaoliang Yuan, Xugang Wang, Qinyu Xu, Haoran Wu

{"title":"KIAA1429 and AlkB Homolog 5 Regulate Bladder Cancer Progression via N6-Methyladenosine-Dependent Modulation of Sonic Hedgehog Signaling.","authors":"Zhimin Jiao, Xiaowu Liu, Xiaoliang Yuan, Xugang Wang, Qinyu Xu, Haoran Wu","doi":"10.1002/mc.70004","DOIUrl":"10.1002/mc.70004","url":null,"abstract":"N6-methyladenosine (m6A) modification plays a pivotal role in cancer progression, yet its regulatory mechanisms in bladder cancer (BCa) remain poorly understood. This study investigates the functions of two key m6A regulators-α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) and KIAA1429-in modulating BCa cell behavior. Expression levels of ALKBH5, KIAA1429, and Sonic Hedgehog (SHH) were examined in BCa tissues and adjacent normal tissues. Functional assays, including methylated RNA immunoprecipitation-quantitative PCR (MeRIP-qPCR), RNA immunoprecipitation (RIP), and RNA stability assessments, were performed in J82 BCa cells to explore the underlying mechanisms. Results revealed that KIAA1429 was significantly upregulated in BCa and promoted cell proliferation, migration, and invasion by enhancing m6A modification and stabilizing SHH mRNA, leading to activation of the Hedgehog signaling pathway. In contrast, ALKBH5, which was downregulated in BCa, acted as an m6A demethylase that destabilized SHH mRNA and attenuated Hedgehog pathway activity, thereby counteracting the oncogenic effects of KIAA1429. Moreover, overexpression of SHH reversed the inhibitory effects induced by KIAA1429 knockdown, confirming its role as a downstream effector. In conclusion, ALKBH5 and KIAA1429 exert opposing regulatory effects on BCa progression via m6A-mediated modulation of SHH expression and Hedgehog signaling. These findings highlight SHH mRNA methylation as a central mechanism in BCa malignancy and identify ALKBH5 and KIAA1429 as potential therapeutic targets.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1473-1486"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497529","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 2区医学

Molecular Carcinogenesis Pub Date : 2025-09-01 Epub 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":"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":"1500-1513"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","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 2区医学

Molecular Carcinogenesis Pub Date : 2025-09-01 Epub 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":"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":"1514-1527"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","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

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 2区医学

Molecular Carcinogenesis Pub Date : 2025-09-01 Epub 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":"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":"1539-1551"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","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