Molecular Carcinogenesis最新文献

{"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":"https://doi.org/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":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-23","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":"Knocking Down Ferredoxin 1 Inhibits the Progression of Colorectal Cancer and Regulates Cuproptosis via Mediating the Hippo Signaling Pathway.","authors":"Ying Hu, Haihua Liu, Xiaobin Tan, Xiongjian Wu","doi":"10.1002/mc.23897","DOIUrl":"https://doi.org/10.1002/mc.23897","url":null,"abstract":"<p><p>Cuproptosis is a form of programmed cell death dependent on mitochondrial respiration and is crucial in cancer treatment. The study attempted to screen cuproptosis-associated genes in colorectal cancer (CRC) and reveal regulatory pathways. Weighted gene co-expression network analysis (WGCNA) was applied to screen the co-expression modules based on gene expression in CRC patients. The cuproptosis-associated genes were screened at the intersection of co-expression modules and cuproptosis gene data set. RNA sequencing was performed to assess the transcriptome changes, followed by functional enrichment analyses to reveal the potential pathways. Ferredoxin 1 (FDX1) was knocked down in in vivo and in vitro experiments to investigate the effects of FDX1 knockdown on CRC progression and cuproptosis. FDX1 was found as a cuproptosis-associated gene and was highly expressed in CRC tumor and CRC cells. Knockdown of FDX1 regulated cuproptosis in CRC cells, and inhibited CRC cell growth, migration and invasion. We screened 1956 upregulated DEGs and 2201 downregulated DEGs in si-FDX1 cells, which were mainly enriched in mitogen-activated protein kinase (MAPK) signaling pathway, tumor necrosis factor (TNF) signaling pathway and Hippo signaling pathway. Knockdown of FDX1 inhibited CRC progression by increasing the levels of dihydrolipoamide S-succinyltransferase (DLST), lipoic acid synthetase (LIAS) and phosphorylation Yes-associated protein (pYAP)/YAP, and downregulated transcriptional coactivator with a PDZ-binding domain (TAZ). The inhibitor of Hippo pathway GA-017 blocked this process. Knocking down FDX1 regulated cuproptosis and inhibited CRC progression by mediating the Hippo signaling pathway, which shed new insights into the development of biomarkers for CRC treatment.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483707","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":"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":"https://doi.org/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":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-17","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}

{"title":"CircST6GALNAC6 Inhibits Glycolysis of Bladder Cancer by Regulating PRKN/HK1 Signaling Pathway.","authors":"Yali Zuo, Da Ren, Haiqing He, Changkun Huang, Xuan Zhu","doi":"10.1002/mc.23894","DOIUrl":"https://doi.org/10.1002/mc.23894","url":null,"abstract":"<p><p>Bladder cancer (BCa) is an aggressive malignancy of urinary system. Aerobic glycolysis refers to the phenomenon wherein cancer cells increase glucose consumption and produce lactic acid. Our study focused on the role and mechanism of circST6GALNAC6 in BCa glycolysis. The 24 h glucose intake was detected using flow cytometry. Lactic acid and ATP were detected in BCa cells utilizing commercially provided kits. Extracellular acidification rate was measured using Seahorse XF-96p Extracellular Flux Analyzer. Cell proliferation was determined using colony formation assay. RNA immunoprecipitation and co-immunoprecipitation experiments were adopted to validate molecular interactions. BALB/C nude mice were utilized to establish xenograft tumor model. CircST6GALNAC6 was decreased in BCa cells, and overexpression of circST6GALNAC6 inhibited glycolysis and proliferation of BCa cells. Additionally, overexpression of circST6GALNAC6 promoted the degradation of glycolytic regulatory protein HK1 and decreased its expression, and PRKN facilitated ubiquitination-related degradation of HK1. CircST6GALNAC6 enhanced the mRNA stability and expression of PRKN by recruiting FUS. Furthermore, the inhibitory impact of circST6GALNAC6 overexpression on glycolysis in BCa cells was reversed by PRKN knockdown. Finally, overexpression of circST6GALNAC6 suppressed tumor growth through increasing PRKN in nude mice. CircST6GALNAC6 suppressed glycolysis in BCa through FUS/PRKN/HK1 axis. Targeting circST6GALNAC6 holds promise as a novel approach for treating BCa.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441531","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":"https://doi.org/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":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/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":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-07","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":"Identification of Interleukin-Related Genes Signature for Prognosis Prediction in Head and Neck Squamous Cell Carcinoma Patients.","authors":"Haojie Yang, Zihao Liu, Zicong Tan, Huimin Luo, Qin Li, Zhongqi Liu, Fengtao Ji","doi":"10.1002/mc.23880","DOIUrl":"https://doi.org/10.1002/mc.23880","url":null,"abstract":"<p><p>This study focused on identifying the interleukin (IL)-related genes that influence the head and neck squamous cell carcinoma (HNSCC) patients' prognosis and response to anticancer therapy in patients with HNSCC. We developed a risk model that included three gene signatures, IL Enhancer Binding Factor 2 (ILF2), IL 36 alpha (IL36A), and IL10, based on differential expression analysis, survival analysis, Least Absolute Shrinkage and Selection Operator (LASSO) analysis, and Cox regression analysis. We found that the low-risk group was scored with higher immune cell infiltration, higher expression of human leukocyte antigen (HLA) family genes and immune checkpoint genes, higher cytolytic activity (CYT), tertiary lymphoid structures (TLS), and CD8A/PD-L1 ratio. In contrast, the high-risk group was scored with higher tumor immune dysfunction and exclusion (TIDE), which implied worse response to immunotherapy and worse prognosis. The results above indicated that the low-risk group had stronger antitumor immunity and better responsiveness to immunotherapy. We also observed a significantly enriched pattern of cancer-related pathways and immune pathways in the comparison of the high-risk and low-risk groups. Furthermore, the high-risk group had higher sensitivity to chemotherapy drugs, which suggested that they might benefit from chemotherapy treatment. Following the results above, we confirmed in HNSCC cell lines and clinical specimens that the level of ILF2 in tumors was significantly higher than that in adjacent tumor tissues. Besides, in vivo and in vitro results both showed that silencing ILF2 might depress tumor growth, invasion, and migration. This study not only provided novel perspectives into the immunological and molecular mechanisms of HNSCC and uncovered IL-related gene signatures for predicting HNSCC patients' prognosis and response to chemotherapy and immunotherapy, but also preliminarily suggested that ILF2 might be an important target in the treatment of HNSCC.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365271","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":"MicroRNA-505-5p/-3p Regulates the Proliferation, Invasion, Apoptosis, and Temozolomide Resistance in Mesenchymal Glioma Stem Cells by Targeting AUF1.","authors":"Souichi Oe, Rio Kakizaki, Sumika Sakamoto, Teruhide Sato, Mikio Hayashi, Haruna Isozaki, Masahiro Nonaka, Hikaru Iwashita, Shinichi Hayashi, Taro Koike, Ryohei Seki-Omura, Yousuke Nakano, Yuki Sato, Yukie Hirahara, Masaaki Kitada","doi":"10.1002/mc.23842","DOIUrl":"10.1002/mc.23842","url":null,"abstract":"<p><p>Mesenchymal glioma stem cells (MES-GSCs) are a major subtype of GSCs that reside within glioma tissues and contribute to metastasis, therapy resistance, and glioma recurrence. However, the precise molecular mechanisms governing MES-GSC functions remain elusive. Our findings revealed that expression levels of miR-505-5p/-3p are elevated in MES-GSCs compared with those in proneural (PN)-GSCs, glioma cell lines, and normal brain tissue and that miR-505-5p/-3p expression levels are decreased in differentiated MES-GSCs. We assumed that miR-505-5p/-3p would play distinctive roles in MES-GSCs and performed loss-of-function experiments targeting miR-505-5p/-3p. Knockdown of miR-505-5p/-3p increased proliferation and promoted differentiation in MES-GSCs while suppressing invasion, temozolomide resistance, and enhancing apoptosis in MES-GSCs. Mechanistically, miR-505-5p/-3p directly targets the 3' UTR of AUF1, leading to its repression in MES-GSCs. Notably, AUF1 expression levels were significantly lower in MES-GSCs compared with those in PN-GSCs, glioma cell lines, and normal brain tissues. Co-inhibition of AUF1 expression with miR-505-5p/-3p knockdown ameliorated the observed cellular phenotypes caused by miR-505-5p/-3p knockdown in MES-GSCs. These results suggest that miR-505-5p/-3p exerts MES-GSC-specific roles in regulating proliferation, differentiation, invasion, apoptosis, and temozolomide resistance by repressing AUF1 expression.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"279-289"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604713","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":"Predictive Value of Neutrophil Extracellular Traps in Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer.","authors":"Bingqing Shang, Zhilong Hu, Ruiyang Xie, Jie Wu, Wang Qu, Wen Zhang, Aiping Zhou, Lin Feng, Xingang Bi, Jianzhong Shou","doi":"10.1002/mc.23844","DOIUrl":"10.1002/mc.23844","url":null,"abstract":"<p><p>Cisplatin-based chemotherapy is the recommended therapy for muscle-invasive bladder cancer (MIBC). However, the efficacy of MIBC for chemotherapy is only about 40%. Therefore, predictors of therapy response are urgently needed. Neutrophils form neutrophil extracellular traps (NETs), a network structure, and growing evidence indicated that it could be a prognostic and predictive marker in cancer. In MIBC, the predictive role of NETs in chemotherapy resistance is unclear. We used the Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression analyses to develop a NETs-associated signature score (NETs-score) for therapeutic response prediction in the discovery cohort (GSE169455). Then the NETs score-based risk stratification was verified in two validation cohorts (Taber et al.'s cohort, our institutional cohort). In the training cohort, high NETs-score was associated with poor chemotherapy response (AUC = 0.781) and reduced recurrence-free survival (RFS) (hazard ratio [HR] = 2.07, 95% confidence interval [CI]: [1.26-3.40], p = 0.003) in MIBC patients. The NETs-score was also demonstrated to be a predictive factor for the efficacy of neoadjuvant chemotherapy in the validation cohort (AUC = 0.731). The accuracy of the NETs-score was superior to other chemotherapy response predictors such as Ba/Sq expression subtype (AUC = 0.711), BRCA2 mutation (AUC = 0.692) and ERCC2 mutation (AUC = 0.548). Furthermore, in our center cohort, the expression level of H3Cit showed a significant difference between the response and no-response group (p = 0.01). Through immunohistochemical validation, NETs was an independent predictor of MIBC neoadjuvant chemotherapy efficacy as determined by the multivariate logistic regression analysis (OR = 5.94, 95% CI: 1.20-45.50, p = 0.045). Patients with high levels of NETs predicted poor response to neoadjuvant chemotherapy. This study was the first to reveal the correlation between the level of NETs in MIBC and the efficacy of chemotherapy, which may provide a theoretical basis regarding NETs inhibitors.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"305-316"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624139","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":"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":"<p><p>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.</p>","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}