Molecular Carcinogenesis最新文献

{"title":"Expression of Concern: Alterations of RASSF1A in Premalignant Cervical Lesions: Clinical and Prognostic Significance.","authors":"","doi":"10.1002/mc.23888","DOIUrl":"10.1002/mc.23888","url":null,"abstract":"","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"952"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046783","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}

{"title":"ARMC10 Drives Glioblastoma Progression Through Activating Notch Pathway.","authors":"Bin Feng, Taihong Gao, Lin Chen, Yi Xing","doi":"10.1002/mc.23895","DOIUrl":"10.1002/mc.23895","url":null,"abstract":"<p><p>This study aimed to check the biological functions and uncover the mechanism of armadillo repeat protein C10 (ARMC10) in glioblastoma (GBM). The expression and potential mechanisms of ARMC10 in GBM were analyzed by bioinformatics analysis. In GBM cells, function-loss experiments were used to evaluate the influences of ARMC10 on cell proliferation, cell invasion, lipid levels, and cell migration by colony formation assay, 5-ethynyl-2'-deoxyuridine staining, cell counting kit-8 assay, transwell assay, BODIPY staining, and wound healing assay. Mouse xenograft models were constructed to validate the influences of ARMC10 in vivo. ARMC10 levels in GBM were upregulated, and patients with low ARMC10 levels displayed a better prognosis. ARMC10 knockdown resulted in a decrease of GBM cell invasion, migration, and proliferation. GSEA showed that ARMC10 was positively associated with the Notch pathway and fatty acid metabolism. ARMC10 knockdown reduced the levels of triglyceride, cholesterol, and lipid, and inhibited the expression of proteins related to fatty acid metabolism and Notch pathway. Moreover, notch receptor 1 (Notch1) overexpression reversed the inhibition of cell proliferation, fatty acid metabolism, and invasion induced by ARMC10 knockdown. In vivo, ARMC10 knockdown suppressed tumor growth. RMC10 knockdown suppressed GBM malignant progression, which had a bearing on Notch pathway.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"883-896"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483699","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}

{"title":"Potential Crosstalk Between ANXA1+ Epithelial Cells and FABP4+ TAM Cells of Ferroptosis-Related Molecular Clusters Promotes an Immunosuppressive Microenvironment in Non-Small Cell Lung Cancer.","authors":"Shengqiang Mao, Qingyan Li, Ying Yang, Zhiqiang Liu, Li Zhang","doi":"10.1002/mc.23899","DOIUrl":"10.1002/mc.23899","url":null,"abstract":"<p><p>The tumor microenvironment (TME) affects tumor initiation, invasion, metastasis, and therapies. Recently, increasing evidence has demonstrated that ferroptosis plays important regulatory roles in tumourigenesis and progression. It is unclear how ferroptosis affects non-small cell lung cancer (NSCLC) progression by remodeling the TME. In this study, the single-cell RNA sequencing (scRNA-seq) data (85,562 cells, n = 18) were employed to reveal the heterogeneity of ferroptosis activation in NSCLC, and identified six ferroptosis-related molecular clusters. We found that ANXA1+ epithelial and FABP4 + TAM subpopulations were key factors in lung cancer progression and TME remodeling. In addition, the cell-cell communication analysis showed that ANXA1-FPR2/FPR1 receptor-ligand pair contributed to the formation of an immunosuppressive TME. Furthermore, we established a novel signature based on ferroptosis-related molecular clusters, and the risk score model may predict survival and response to immunotherapy. We also found that compared with responder, the expression of ANXA1 and FABP4 is higher in progressor, which indicating a higher expression of ANXA1 and FABP4 was associated with a worse response to immunotherapy. Therefore, we concluded that the molecular clusters associated with ferroptosis served as potential prognostic markers and therapeutic targets for NSCLC patients.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"936-950"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557486","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}

{"title":"SPP1 Promotes NSCLC Brain Metastasis Via Sequestration of Ubiquitin Ligase RNF114 to Facilitate P85α Ubiquitination.","authors":"Xiaoqin Li, Yun Wu, Baosong Xie, Mingxiao Xu, Tianjian Xie, Wenxiang Yue, Ming Lin, Ying Lin, Yusheng Chen","doi":"10.1002/mc.23866","DOIUrl":"10.1002/mc.23866","url":null,"abstract":"<p><p>Brain metastasis (BM) is a significant factor contributing to the poor prognosis of patients with non-small cell lung cancer (NSCLC). Secreted phosphoprotein 1 (SPP1) is implicated in the progression and metastasis of several cancers. The role of SPP1 in NSCLC remains unclear, especially in NSCLC BM. This study aimed to identify genes associated with NSCLC BM and to investigate the involvement of SPP1 in NSCLC BM. Integrated genomic analysis was utilized to identify candidate genes in NSCLC. The expression levels of SPP1 were evaluated in NSCLC tissues and cell lines. In vitro and in vivo experiments were conducted to assess the effect of SPP1 on NSCLC cell behavior and BM. The potential mechanisms of SPP1 were demonstrated by CO-IP and liquid chromatography-mass spectrometry (LC-MS). The underlying mechanism involving the PI3K/AKT/mTOR pathway was explored. The results showed that SPP1 expression was upregulated in NSCLC tissues and cell lines. Depletion of SPP1 using shRNA inhibited cell proliferation, migration, and invasion in vitro and suppressed BM in vivo. Mechanistically, SPP1 facilitates the ubiquitination of P85α by interacting with the ubiquitin ligase RNF114, thus playing a role in regulating NSCLC BM through the PI3K/AKT/mTOR signaling pathway. Moreover, immunohistochemistry staining confirmed higher expression of SPP1 in NSCLC tissues with BM compared to those without BM. In summary, elevated SPP1 expression was associated with poor clinical outcomes in NSCLC patients. This study highlights the role of SPP1 as a regulator of cell metastasis and suggests its potential as a novel therapeutic target for BM in NSCLC.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"829-841"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365273","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}

{"title":"CircDIAPH1 Promotes Liver Metastasis and Development of Colorectal Cancer by Initiation of CEACAM6 Expression.","authors":"Wei Wang, Xu Li, Hantao Wang, Cheng Huang, Laicheng Zhu, Hao Wang, Wei Zhang","doi":"10.1002/mc.23896","DOIUrl":"10.1002/mc.23896","url":null,"abstract":"<p><p>Liver metastasis is a critical factor influencing the 5-year survival rate in colorectal cancer (CRC). However, the biological function of most circRNAs in liver metastasis of CRC is still unknown. In this study, we identified differentially expressed circRNAs associated with liver metastasis (LM-DE-circRNAs). A total of 247 LM-DE-circRNAs were identified, and crucial signaling pathways, including the regulation of actin cytoskeleton, were significantly enriched, featuring six LM-DE-circRNAs. Notably, circDIAPH1 (hsa_circ_0074323), with the highest AUC value, emerged as a potential biomarker for CRC liver metastasis (CRLM). Functional assays following circDIAPH1 knockdown demonstrated induced apoptosis, suppressed proliferation, reduced metastasis, and invasion in CRC cell lines in vitro. The circDIAPH1 knockdown attenuated tumor growth in a cell-derived xenograft model. Furthermore, circDIAPH1 knockdown lessened the liver metastasis. Transcriptome profiling revealed that CEACAM6 was the most downregulated gene while circDIAPH1 was knocked down, and possesses high expression value in CRC. Most importantly, we found that circDIAPH1 recruited transcription factor FOXA1 to bind in the promoter region of CEACAM6 and initiated CEACAM6 expression. Additionally, the study identified the transcription factor BRD4 as a regulator of circDIAPH1 expression in CRC. In conclusion, this study reveals that circDIAPH1 recruits FOXA1 to initiate CEACAM6 expression, promoting liver metastasis and development of CRC.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"897-910"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483702","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}

{"title":"Expression of Concern: Amplification of Cyclinl1 in Uterine Cervical Carcinoma Has Prognostic Implications.","authors":"","doi":"10.1002/mc.23887","DOIUrl":"10.1002/mc.23887","url":null,"abstract":"","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"951"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033682","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}

{"title":"The Role of HADHB in Mitochondrial Fatty Acid Metabolism During Initiation of Metastasis in ccRCC.","authors":"Xin Li, Mengmeng Wu, Guijuan Chen, Wenliang Ma, Yi Chen, Yibing Ding, Ping Dong, Weidong Ding, Luqing Zhang, Lei Yang, Weidong Gan, Dongmei Li","doi":"10.1002/mc.23898","DOIUrl":"10.1002/mc.23898","url":null,"abstract":"<p><p>The initiation and progression of clear cell renal cell carcinoma (ccRCC) are closely linked to significant metabolic alterations. Specifically, lipid metabolism alterations and their association with the high invasiveness in ccRCC require further investigation. After conducting RNA-sequencing (RNA-seq), we discovered that Hydroxyacyl-CoA Dehydrogenase Trifunctional Multienzyme Complex Subunit Beta (HADHB) was significantly downregulated in the highly invasive ccRCC cell line. It was found that the expression of HADHB in ccRCC tumor tissues was lower than that in paracancer tissues, which is associated with poor patient prognosis. Subsequently, we confirmed that highly invasive ccRCC exhibited an increased lipid accumulation due to the suppression of mitochondrial fatty acid transport and enhanced conversion of fatty acids to triglycerides within cancer cells. Specifically, the downregulation of HADHB inhibited mitochondrial fatty acid β-oxidation (FAO) in cancer cells, leading to partial impairment of mitochondrial function and decreased ATP production. However, this trade-off involving the reduction of a high-yield ATP production conferred an advantage by reducing reactive oxygen species (ROS) generation within cancer cells, thereby protecting them from oxidative stress and enhancing their invasive potential. Furthermore, the downregulation of HADHB promoted epithelial-mesenchymal transition (EMT) and angiogenesis in cancer cells, accelerating the progression of ccRCC and endowing ccRCC cells with metastatic capabilities.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"923-935"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483708","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}

{"title":"Sophoricoside Inhibited Glioblastoma Cell Progression Through Activated AMP-Activated Protein Kinase (AMPK).","authors":"Changquan Wang, Xuehui Xiong, Chang Li, Yuan Lu, Yan Zhang, Han Tian, Chunlin Xu, Tengfei Ma, Jinhua Wang, Jianqing Zhang, Lei Wang","doi":"10.1002/mc.23889","DOIUrl":"10.1002/mc.23889","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most common malignant primary brain tumor, with a mean survival of less than 2 years. Unique brain structures and the microenvironment, including blood-brain barriers, put great challenges on clinical drug development. Sophoricoside (Sop), an isoflavone glycoside isolated from seeds of Sophora japonica L., is one of the active constituents of traditional Chinese medicine and found to inhibit the bioactivity of cytokines (e.g., interleukin-5) and inflammatory responses, as well as to attenuate glucose and lipid metabolism in related diseases. However, the effects of Sop on cancer progression have not been systemically investigated. In this study, we performed a comprehensive investigation of Sop's function in GBM using colony formation and Transwell assays in vitro, along with subcutaneous xenograft tumor analysis in vivo. We employed RNA sequencing and bioinformatics analysis in conjunction with Western blotting (WB) and reverse transcription-quantitative polymerase chain reaction (RT-PCR) to explore the underlying mechanism. Our results demonstrated that Sop suppressed U251 cell proliferation and metastasis in vitro and inhibited the tumorigenic behavior of U251 cells in vivo. Further investigations revealed a positive correlation between the levels of activated AMP-activated protein kinase (AMPK) and Sop treatment; notably the application of the AMPK inhibitor, compound C (CC), abolished inhibitory effects of Sop on the malignant phenotype of U251 cells. These findings suggest the potential application of Sop in GBM treatment and highlight opportunities for the development of new therapeutic strategies.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"816-828"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059701","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}

{"title":"Evaluation and Comparison of Prognostic Multigene Tests in Early-Stage Breast Cancer: Which Is the Most Effective? A Literature Review Exploring Clinical Utility to Enhance Therapeutic Management in Luminal Patients.","authors":"Marianna Rita Brogna, Gerardo Ferrara, Valeria Varone, Angela Montone, MariaRosaria Schiano, Michele DelSesto, Francesca Collina","doi":"10.1002/mc.23893","DOIUrl":"10.1002/mc.23893","url":null,"abstract":"<p><p>Breast cancer is the most common malignancy affecting women, marked by significant complexity and heterogeneity. This disease includes multiple subtypes, each with unique biological features and treatment responses. Despite significant advancements in detection and therapy, challenges remain, particularly in managing aggressive forms like triple-negative breast cancer and overcoming drug resistance. Breast cancer classification and subtype determination are typically performed by immunohistochemistry (IHC) method, which assesses four key markers (ER, PR, HER2, KI67); however, due to the recognized issues with this approach-especially regarding the evaluation of Ki67-there is a risk of misclassification. Patients who may be suitable for chemotherapy could miss possible advantages and only experience needless toxicity as a result of improper treatment decisions. Molecular profiling has improved breast cancer management, enabling the creation of multigene prognostic tests (MPTs) like Oncotype Dx, MammaPrint, Prosigna, Endopredict, and Breast Cancer Index which assess gene expression profiles to more accurately predict recurrence risks. These tools help personalize treatment, identifying patients who can avoid chemotherapy and/or extended endocrine therapy. While many MPTs are available, only Oncotype Dx and MammaPrint have prospective validation, with Prosigna providing additional prognostic insights by incorporating clinical variables. Molecular tests are especially usefull in the \"gray zone,\" which includes tumors measuring between 1 and 3 cm with 0-3 positive lymph nodes and an intermediate proliferation index. However, their clinical utility has not been definitively established, and significant differences exist between them. This article provides an in-depth analysis of established genomic assays, including testing procedures, clinical validity, utility, diagnostic frameworks, and methodologies. Our comparison aims to improve early breast cancer management by guiding pathologists and oncologists in optimizing the use of genomic assays in clinical practice. By presenting this information, we aim to enhance understanding of the clinical utility and effectiveness of these assays, supporting the development of personalized treatment strategies for early breast cancer patients. Genomic assays offer important insights that can support treatment decisions in early-stage breast cancer, especially when used alongside other clinical evaluations, predictive tools, and management guidelines. While multiple gene expression profiling tests are available, they classify patients differently and are not interchangeable; therefore, their application should be at the clinician's discretion during the decision-making process. It is essential that these tests are not the sole factor in determining the best treatment plan: other clinical considerations and patient preferences should also play a significant role in guiding treatment decisions.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"789-800"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL1 Enhances RRP9 mRNA Stability Through m7G Modification to Drive Colorectal Tumorigenesis.","authors":"Nan Li, Ying Jing, Long Xu, Maonan Wang","doi":"10.1002/mc.23892","DOIUrl":"10.1002/mc.23892","url":null,"abstract":"<p><p>METTL1, a well-established RNA methyltransferase for the N(7)-methylguanosine (m7G) methylation modification, is responsible for human tumorigenesis. Here, we aimed to examine the activity and molecular determinants of METTL1 in colorectal cancer (CRC) development. METTL1 and ribosomal RNA processing 9 (RRP9) mRNA analysis was performed by quantitative PCR. Protein expression was detected by immunoblotting and immunohistochemistry (IHC). Cell sphere formation, invasion, and proliferation were assessed by sphere formation, transwell, and MTT assays, respectively. Cell migration was tested by transwell and wound healing assays. Subcutaneous xenografts were produced to analyze the role in vivo. The influence of METTL1 in m7G methylation and stability of RRP9 mRNA was evaluated by methylated immunoprecipitation (MeRIP) assay and Actinomycin D (Act D) treatment, respectively. METTL1 was highly expressed in CRC tumors and cell lines. METTL1 depletion suppressed CRC cell proliferation, invasiveness, migratory ability, and sphere formation potential in vitro, while increased METTL1 expression had opposite effects. METTL1 positively correlated with RRP9 expression in CRC. Mechanistically, METTL1 promoted RRP9 mRNA stability by mediating its m7G methylation, and METTL1 regulated the PI3K/AKT signaling by RRP9. Increased RRP9 expression partially reversed the suppressive effects of METTL1 depletion on CRC cell phenotypes in vitro. METTL1 depletion impeded the growth of HCT-116 subcutaneous xenografts in vivo by RRP9. Our observations identified METTL1 as a crucial protumorigenic factor to drive growth, metastasis, and stemness of CRC cells through RRP9, offering new targets for combating CRC.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"858-869"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440512","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}