Molecular Cancer最新文献

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Distant origin of glioblastoma recurrence: neural stem cells in the subventricular zone serve as a source of tumor reconstruction after primary resection 胶质母细胞瘤复发的远端起源:脑室下区的神经干细胞是原发切除术后肿瘤重建的源头
IF 37.3 1区 医学
Molecular Cancer Pub Date : 2025-03-04 DOI: 10.1186/s12943-025-02273-2
Xue Li, Hyun Jung Kim, Jihwan Yoo, Yeonhee Lee, Chang Hyun Nam, Jonghan Park, Soon-Tae Lee, Tae Min Kim, Seung Hong Choi, Jae-Kyung Won, Sung‑Hye Park, Young Seok Ju, Jong Bae Park, Se Hoon Kim, Jong Hee Chang, Hong-Gyun Wu, Chul-Kee Park, Jeong Ho Lee, Seok-Gu Kang, Joo Ho Lee
{"title":"Distant origin of glioblastoma recurrence: neural stem cells in the subventricular zone serve as a source of tumor reconstruction after primary resection","authors":"Xue Li, Hyun Jung Kim, Jihwan Yoo, Yeonhee Lee, Chang Hyun Nam, Jonghan Park, Soon-Tae Lee, Tae Min Kim, Seung Hong Choi, Jae-Kyung Won, Sung‑Hye Park, Young Seok Ju, Jong Bae Park, Se Hoon Kim, Jong Hee Chang, Hong-Gyun Wu, Chul-Kee Park, Jeong Ho Lee, Seok-Gu Kang, Joo Ho Lee","doi":"10.1186/s12943-025-02273-2","DOIUrl":"https://doi.org/10.1186/s12943-025-02273-2","url":null,"abstract":"Glioblastoma (GBM) is the most aggressive and common type of primary malignant brain cancer in adults. GBM often recurs locally near the resection cavity (RC) following the surgical removal of primary tumors. Recent research has reported that neural stem cells (NSCs) in the subventricular zone (SVZ) harboring cancer-driving mutations serve as the cells of origin for human GBM. However, the pathological role of tumor-initiating NSCs in the SVZ in tumor recurrence remains to be elucidated. Here, we explore the potential contribution of mutation-harboring NSCs in the SVZ to tumor recurrence around the RC following surgical resection. Our hypothesis emerged from performing deep sequencing of longitudinal tissues from 10 patients with GBM, including (i) tumor-free SVZ tissue, (ii) primary tumor tissue, (iii) recurrent tumor tissue, and (iv) blood. As a result of this sequencing, we observed evidence suggesting that recurrent tumors show genetic links to the SVZ in 60% (6/10) of patients, which are distinct from the primary tumors. Using a genome-edited mouse model, we further identified that mutation-harboring NSCs appeared to migrate to the RC through the aberrant growth of oligodendrocyte progenitor cells, potentially contributing to the reconstruction of high-grade malignant gliomas in the RC. This process was associated with the CXCR4/CXCL12 axis, as supported by RNA sequencing data from human recurrent GBM. Taken together, our findings suggest that NSCs in human SVZ tissue may play a role in GBM recurrence, potentially highlighting a novel distant contributor of recurrence.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"96 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Nanobodies targeting the tumor microenvironment and their formulation as nanomedicines 靶向肿瘤微环境的纳米体及其作为纳米药物的配方
IF 37.3 1区 医学
Molecular Cancer Pub Date : 2025-03-04 DOI: 10.1186/s12943-025-02270-5
Liudmyla Maksymova, Yannick A. Pilger, Lutz Nuhn, Jo A. Van Ginderachter
{"title":"Nanobodies targeting the tumor microenvironment and their formulation as nanomedicines","authors":"Liudmyla Maksymova, Yannick A. Pilger, Lutz Nuhn, Jo A. Van Ginderachter","doi":"10.1186/s12943-025-02270-5","DOIUrl":"https://doi.org/10.1186/s12943-025-02270-5","url":null,"abstract":"Among the emerging strategies for cancer theranostics, nanomedicines offer significant promise in advancing both patients’ diagnosis and treatment. In combination with nanobodies, nanomedicines can potentially enhance the precision and efficiency of drug or imaging agent delivery, addressing key limitations of current approaches, such as off-target toxicities. The development of nanomedicines will be further accelerated by the creation of smart nanoparticles, and their integration with immunotherapy. Obviously, the success of nano-immunotherapy will depend on a comprehensive understanding of the tumor microenvironment, including the complex interplay of mechanisms that drive cancer-mediated immunosuppression and immune escape. Hence, effective therapeutic targeting of the tumor microenvironment requires modulation of immune cell function, overcoming resistance mechanisms associated with stromal components or the extracellular matrix, and/or direct elimination of cancer cells. Identifying key molecules involved in cancer progression and drug resistance is, therefore, essential for developing effective therapies and diagnostic tools that can predict patient responses to treatment and monitor therapeutic outcomes. Current nanomedicines are being designed with careful consideration of factors such as the choice of carrier (e.g., biocompatibility, controlled cargo release) and targeting moiety. The unique properties of nanobodies make them an effective engineering tool to target biological molecules with high affinity and specificity. In this review, we focus on the latest applications of nanobodies for targeting various components of the tumor microenvironment for diagnostic and therapeutic purposes. We also explore the main types of nanoparticles used as a carrier for cancer immunotherapies, as well as the strategies for formulating nanoparticle-nanobody conjugates. Finally, we highlight how nanobody-nanoparticle formulations can enhance current nanomedicines.\u0000","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"34 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Lipid metabolic reprograming: the unsung hero in breast cancer progression and tumor microenvironment 脂质代谢重编程:乳腺癌进展和肿瘤微环境中的无名英雄
IF 37.3 1区 医学
Molecular Cancer Pub Date : 2025-03-03 DOI: 10.1186/s12943-025-02258-1
Mengting Wan, Shuaikang Pan, Benjie Shan, Haizhou Diao, Hongwei Jin, Ziqi Wang, Wei Wang, Shuya Han, Wan Liu, Jiaying He, Zihan Zheng, Yueyin Pan, Xinghua Han, Jinguo Zhang
{"title":"Lipid metabolic reprograming: the unsung hero in breast cancer progression and tumor microenvironment","authors":"Mengting Wan, Shuaikang Pan, Benjie Shan, Haizhou Diao, Hongwei Jin, Ziqi Wang, Wei Wang, Shuya Han, Wan Liu, Jiaying He, Zihan Zheng, Yueyin Pan, Xinghua Han, Jinguo Zhang","doi":"10.1186/s12943-025-02258-1","DOIUrl":"https://doi.org/10.1186/s12943-025-02258-1","url":null,"abstract":"Aberrant lipid metabolism is a well-recognized hallmark of cancer. Notably, breast cancer (BC) arises from a lipid-rich microenvironment and depends significantly on lipid metabolic reprogramming to fulfill its developmental requirements. In this review, we revisit the pivotal role of lipid metabolism in BC, underscoring its impact on the progression and tumor microenvironment. Firstly, we delineate the overall landscape of lipid metabolism in BC, highlighting its roles in tumor progression and patient prognosis. Given that lipids can also act as signaling molecules, we next describe the lipid signaling exchanges between BC cells and other cellular components in the tumor microenvironment. Additionally, we summarize the therapeutic potential of targeting lipid metabolism from the aspects of lipid metabolism processes, lipid-related transcription factors and immunotherapy in BC. Finally, we discuss the possibilities and problems associated with clinical applications of lipid‑targeted therapy in BC, and propose new research directions with advances in spatiotemporal multi-omics.\u0000","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"66 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
From morphology to single-cell molecules: high-resolution 3D histology in biomedicine 从形态学到单细胞分子:生物医学中的高分辨率3D组织学
IF 37.3 1区 医学
Molecular Cancer Pub Date : 2025-03-03 DOI: 10.1186/s12943-025-02240-x
Xintian Xu, Jimeng Su, Rongyi Zhu, Kailong Li, Xiaolu Zhao, Jibiao Fan, Fengbiao Mao
{"title":"From morphology to single-cell molecules: high-resolution 3D histology in biomedicine","authors":"Xintian Xu, Jimeng Su, Rongyi Zhu, Kailong Li, Xiaolu Zhao, Jibiao Fan, Fengbiao Mao","doi":"10.1186/s12943-025-02240-x","DOIUrl":"https://doi.org/10.1186/s12943-025-02240-x","url":null,"abstract":"High-resolution three-dimensional (3D) tissue analysis has emerged as a transformative innovation in the life sciences, providing detailed insights into the spatial organization and molecular composition of biological tissues. This review begins by tracing the historical milestones that have shaped the development of high-resolution 3D histology, highlighting key breakthroughs that have facilitated the advancement of current technologies. We then systematically categorize the various families of high-resolution 3D histology techniques, discussing their core principles, capabilities, and inherent limitations. These 3D histology techniques include microscopy imaging, tomographic approaches, single-cell and spatial omics, computational methods and 3D tissue reconstruction (e.g. 3D cultures and spheroids). Additionally, we explore a wide range of applications for single-cell 3D histology, demonstrating how single-cell and spatial technologies are being utilized in the fields such as oncology, cardiology, neuroscience, immunology, developmental biology and regenerative medicine. Despite the remarkable progress made in recent years, the field still faces significant challenges, including high barriers to entry, issues with data robustness, ambiguous best practices for experimental design, and a lack of standardization across methodologies. This review offers a thorough analysis of these challenges and presents recommendations to surmount them, with the overarching goal of nurturing ongoing innovation and broader integration of cellular 3D tissue analysis in both biology research and clinical practice.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"101 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
BCL-2 dependence is a favorable predictive marker of response to therapy for chronic lymphocytic leukemia BCL-2依赖性是慢性淋巴细胞白血病治疗反应的良好预测指标
IF 37.3 1区 医学
Molecular Cancer Pub Date : 2025-03-03 DOI: 10.1186/s12943-025-02260-7
Stephen Jun Fei Chong, Junyan Lu, Rebecca Valentin, Timothy Z. Lehmberg, Jie Qing Eu, Jing Wang, Fen Zhu, Li Ren Kong, Stacey M. Fernandes, Jeremy Zhang, Charles Herbaux, Boon Cher Goh, Jennifer R. Brown, Carsten U. Niemann, Wolfgang Huber, Thorsten Zenz, Matthew S. Davids
{"title":"BCL-2 dependence is a favorable predictive marker of response to therapy for chronic lymphocytic leukemia","authors":"Stephen Jun Fei Chong, Junyan Lu, Rebecca Valentin, Timothy Z. Lehmberg, Jie Qing Eu, Jing Wang, Fen Zhu, Li Ren Kong, Stacey M. Fernandes, Jeremy Zhang, Charles Herbaux, Boon Cher Goh, Jennifer R. Brown, Carsten U. Niemann, Wolfgang Huber, Thorsten Zenz, Matthew S. Davids","doi":"10.1186/s12943-025-02260-7","DOIUrl":"https://doi.org/10.1186/s12943-025-02260-7","url":null,"abstract":"Established genetic biomarkers in chronic lymphocytic leukemia (CLL) have been useful in predicting response to chemoimmunotherapy but are less predictive of response to targeted therapies. With several such targeted therapies now approved for CLL, identifying novel, non-genetic predictive biomarkers of response may help to select the optimal therapy for individual patients. We coupled data from a functional precision medicine technique called BH3-profiling, which assesses cellular cytochrome c loss levels as indicators for survival dependence on anti-apoptotic proteins, with multi-omics data consisting of targeted and whole-exome sequencing, genome-wide DNA methylation profiles, RNA-sequencing, protein and functional analyses, to identify biomarkers for treatment response in CLL patients. We initially studied 73 CLL patients from a discovery cohort. We found that greater dependence on the anti-apoptotic BCL-2 protein was associated with prognostically favorable genetic biomarkers. Furthermore, BCL-2 dependence was strongly associated with gene expression patterns and signaling pathways that suggest a more targeted drug-sensitive milieu and was predictive of drug responses. We subsequently demonstrated that these associations were causal in cell lines and additional CLL patient samples. To validate the findings from our discovery cohort and in vitro studies, we utilized primary CLL cells from 54 additional patients treated on a prospective, phase-2 clinical trial of the BTK inhibitor ibrutinib given in combination with chemoimmunotherapy (fludarabine, cyclophosphamide, rituximab) and confirmed in this independent dataset that higher BCL-2 dependence predicted favorable clinical response, independent of the genetic background of the CLL cells. We comprehensively defined BCL-2 dependence as a potential functional and predictive biomarker of treatment response in CLL, underscoring the importance of characterizing apoptotic signaling in CLL to stratify patients beyond genetic markers and identifying novel combinations to exploit BCL-2 dependence therapeutically. Our approach has the potential to help optimize targeted therapy combinations for CLL patients. ","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"23 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 blood-derived exosomal tumor RNA signatures as noninvasive diagnostic biomarkers for multi-cancer: a multi-phase, multi-center study 鉴定血源性外泌体肿瘤RNA特征作为多种癌症的无创诊断生物标志物:一项多期、多中心的研究
IF 37.3 1区 医学
Molecular Cancer Pub Date : 2025-03-01 DOI: 10.1186/s12943-025-02271-4
Fubo Wang, Chengbang Wang, Shaohua Chen, Chunmeng Wei, Jin Ji, Yan Liu, Leifeng Liang, Yifeng Chen, Xing Li, Lin Zhao, Xiaolei Shi, Yu Fang, Weimin Lu, Tianman Li, Zhe Liu, Wenhao Lu, Tingting Li, Xiangui Hu, Mugan Li, Fuchen Liu, Xing He, Jiannan Wen, Zuheng Wang, Wenxuan Zhou, Zehui Chen, Yonggang Hong, Shaohua Zhang, Xiao Li, Rongbin Zhou, Linjian Mo, Duobing Zhang, Tianyu Li, Qingyun Zhang, Li Wang, Xuedong Wei, Bo Yang, Shenglin Huang, Huiyong Zhang, Guijian Pang, Liu Ouyang, Zhenguang Wang, Jiwen Cheng, Bin Xu, Zengnan Mo
{"title":"Identification of blood-derived exosomal tumor RNA signatures as noninvasive diagnostic biomarkers for multi-cancer: a multi-phase, multi-center study","authors":"Fubo Wang, Chengbang Wang, Shaohua Chen, Chunmeng Wei, Jin Ji, Yan Liu, Leifeng Liang, Yifeng Chen, Xing Li, Lin Zhao, Xiaolei Shi, Yu Fang, Weimin Lu, Tianman Li, Zhe Liu, Wenhao Lu, Tingting Li, Xiangui Hu, Mugan Li, Fuchen Liu, Xing He, Jiannan Wen, Zuheng Wang, Wenxuan Zhou, Zehui Chen, Yonggang Hong, Shaohua Zhang, Xiao Li, Rongbin Zhou, Linjian Mo, Duobing Zhang, Tianyu Li, Qingyun Zhang, Li Wang, Xuedong Wei, Bo Yang, Shenglin Huang, Huiyong Zhang, Guijian Pang, Liu Ouyang, Zhenguang Wang, Jiwen Cheng, Bin Xu, Zengnan Mo","doi":"10.1186/s12943-025-02271-4","DOIUrl":"https://doi.org/10.1186/s12943-025-02271-4","url":null,"abstract":"Cancer remains a leading global cause of mortality, making early detection crucial for improving survival outcomes. The study aims to develop a machine learning-enabled blood-derived exosomal RNA profiling platform for multi-cancer detection and localization. In this multi-phase, multi-center study, we analyzed RNA from exosomes derived from peripheral blood plasma in 818 participants across eight cancer types during the discovery phase. Machine learning techniques were applied to identify potential pan-cancer biomarkers. During the screening and model validation phases, the sample size was progressively expanded to 1,385 participants in two steps, while the candidate biomarkers were refined into a set of 12 exosomal tumor RNA signatures (ETR.sig). In the subsequent model construction phase, diagnostic models were developed using the expanded cohort and ETR.sig. Statistical analyses included the calculation of receiver operating characteristic (ROC) curves and AUC values to assess the models' ability to distinguish cancer cases from controls and determine tumor origins. To further validate and explore the biological relevance of the identified biomarkers, we integrated tissue RNA-seq, single-cell data, and clinical information. Machine learning analysis initially identified 33 candidate biomarkers, which were narrowed down to 20 ETR.sig in the screening phase and 12 ETR.sig in the validation phase. In the model construction phase, a diagnostic model based on ETR.sig, built using the Random Forest (RF) algorithm, showed excellent performance with an AUC of 0.915 for distinguishing pan-cancer from controls. The multi-class classification model also demonstrated strong classification power, with macro-average and micro-average AUCs of 0.983 and 0.985, respectively, for differentiating between eight cancer types. Additionally, tumor origin classification using the RF-based diagnostic models achieved high AUC values: BRCA 0.976, COAD 0.98, KIRC 0.947, LIHC 0.967, LUAD 0.853, OV 0.972, PAAD 0.977, and PRAD 0.898. Integration of tissue RNA-seq, single-cell data, and clinical information revealed key associations between ETR.sig-related genes and tumor development. The study demonstrates the robust potential of exosomal RNA as a minimally invasive biomarker resource for cancer detection. The developed ETR.sig platform offers a promising tool for precision oncology and broad-spectrum cancer screening, integrating advanced computational models with nanoscale vesicle biology for accurate and rapid diagnosis.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"28 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Hsa_circ_0125356 promotes gemcitabine resistance by modulating WNT canonical and non-canonical pathways via miR-582-5p/FGF9 axis in non-small cell lung cancer
IF 37.3 1区 医学
Molecular Cancer Pub Date : 2025-02-27 DOI: 10.1186/s12943-025-02259-0
Xinyue Du, Weijie Luo, Hongwu Li, Qi Gu, Ping Huang, Cheng Wang, Na Li, Fanglan Liu, Chunhua Xia
{"title":"Hsa_circ_0125356 promotes gemcitabine resistance by modulating WNT canonical and non-canonical pathways via miR-582-5p/FGF9 axis in non-small cell lung cancer","authors":"Xinyue Du, Weijie Luo, Hongwu Li, Qi Gu, Ping Huang, Cheng Wang, Na Li, Fanglan Liu, Chunhua Xia","doi":"10.1186/s12943-025-02259-0","DOIUrl":"https://doi.org/10.1186/s12943-025-02259-0","url":null,"abstract":"Non-small cell lung cancer (NSCLC) is the leading cause of cancer morbidity and mortality worldwide. The prognosis of patients has been significantly improved by chemotherapy, but acquired drug resistance remains a major obstacle to NSCLC treatment. Circular RNAs (circRNAs), which act as miRNA or protein sponges, are critically associated with the development and chemotherapy resistance of NSCLC. CircRNA sequencing was performed to analyze the differential expression of circRNAs between A549 and A549-GR cells. Chromogenic in situ hybridization (CISH) and immunohistochemistry (IHC) technologies were used to detect the expression of hsa_circ_0125356, miR-582-5p,and FGF9 in NSCLC tissues and para-carcinoma tissues. Fluorescence in situ hybridization (FISH), dual-luciferase reporter assays and RNA immunoprecipitation (RIP) were conducted to evaluate the expression and regulation of hsa_circ_0125356, miR-582-5p, and FGF9. Furthermore, the regulation of hsa_circ_0125356/miR-582-5p/FGF9 on gemcitabine sensitivity was confirmed by TUNEL, Transwell, EdU, CCK8 and immunohistochemistry. We identified a novel hsa_circ_0125356 as a therapeutic target against gemcitabine resistance. Hsa_circ_0125356 was significantly elevated in clinical samples of patients with NSCLC. Moreover, hsa_circ_0125356 overexpression promoted gemcitabine resistance to NSCLC by upregulating FGF9 via sponging miR-582-5p in vivo and in vitro. Notably, WNT canonical (ERK/GSK3β/β-catenin) and non-canonical (Daam1/RhoA/ROCK2) signaling pathways were activated due to hsa_circ_0125356 acting as an endogenous miR-582-5p sponge to regulate the expression of FGF9, and thereby enhancing gemcitabine resistance via promoting DNA damage repair and inhibition of apoptosis. The results were further confirmed by two small molecule antagonists, WAY 316606 and XAV-939,which could inhibit the activation of WNT signaling pathway induced by hsa_circ_0125356. We first demonstrated that hsa_circ_0125356 was significantly upregulated and served as a biomarker for gemcitabine resistance in NSCLC by sponging miR-582-5p/FGF9 axis to regulate the WNT canonical and non-canonical signaling pathways, which provided a new direction for identification of therapeutic targets for the treatment of gemcitabine resistance of NSCLC.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"12 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143507043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
EIF4E-mediated biogenesis of circPHF14 promotes the growth and metastasis of pancreatic ductal adenocarcinoma via Wnt/β-catenin pathway
IF 37.3 1区 医学
Molecular Cancer Pub Date : 2025-02-26 DOI: 10.1186/s12943-025-02262-5
Zhou Fang, Zhuo Wu, Chao Yu, Qingyu Xie, Liangtang Zeng, Rufu Chen
{"title":"EIF4E-mediated biogenesis of circPHF14 promotes the growth and metastasis of pancreatic ductal adenocarcinoma via Wnt/β-catenin pathway","authors":"Zhou Fang, Zhuo Wu, Chao Yu, Qingyu Xie, Liangtang Zeng, Rufu Chen","doi":"10.1186/s12943-025-02262-5","DOIUrl":"https://doi.org/10.1186/s12943-025-02262-5","url":null,"abstract":"CircRNAs are critically involved in the development and progression of various cancers. However, their functions and mechanisms in pancreatic ductal adenocarcinoma (PDAC) remain largely unknown. CircPHF14 (hsa_circ_0079440) was identified through the analysis of RNA sequencing data from PDAC and normal adjacent tissues. The biological functions of circPHF14 were then evaluated using CCK8, EdU, transwell, colony formation, wound healing assays, as well as pancreatic orthotopic xenograft and liver metastasis models. The interaction mechanisms between circPHF14 and PABPC1, which enhance the stability of WNT7A mRNA, were investigated through RNA pull-down, mass spectrometry, RNA Immunoprecipitation (RIP), and actinomycin D assays. The role of EIF4E in promoting circPHF14 biogenesis was examined using RIP, and western blotting. In this study, we observed a significant upregulation of circPHF14 in both clinical PDAC samples and cell lines. Functionally, circPHF14 enhanced PDAC proliferation and metastasis both in vitro and in vivo. Mechanistically, circPHF14 interacted with PABPC1 to stabilize WNT7A mRNA, thereby activating the Wnt/β-catenin pathway, which subsequently upregulated SNAI2 and initiated Epithelial-Mesenchymal Transition (EMT) in PDAC. Additionally, EIF4E was found to bind PHF14 pre-mRNA, facilitating circPHF14 biogenesis. Finally, we developed a lipid nanoparticle (LNP) formulation encapsulating sh-circPHF14 plasmids and confirmed its anti-tumor efficacy in a patient-derived xenograft (PDX) model. EIF4E-mediated biogenesis of circPHF14 stabilizes WNT7A mRNA via interaction with PABPC1, which subsequently activates the Wnt/β-catenin pathway, promoting the growth and metastasis of PDAC. These findings indicate that circPHF14 holds promise as a biomarker and therapeutic target for PDAC.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"10 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Glioblastoma multiforme: insights into pathogenesis, key signaling pathways, and therapeutic strategies 多形性胶质母细胞瘤:对发病机制、关键信号通路和治疗策略的见解
IF 37.3 1区 医学
Molecular Cancer Pub Date : 2025-02-26 DOI: 10.1186/s12943-025-02267-0
Ashkan Pouyan, Masoud Ghorbanlo, Masoud Eslami, Majid Jahanshahi, Ehsan Ziaei, Ali Salami, Khatere Mokhtari, Koorosh Shahpasand, Najma Farahani, Tohid Emami Meybodi, Maliheh Entezari, Afshin Taheriazam, Kiavash Hushmandi, Mehrdad Hashemi
{"title":"Glioblastoma multiforme: insights into pathogenesis, key signaling pathways, and therapeutic strategies","authors":"Ashkan Pouyan, Masoud Ghorbanlo, Masoud Eslami, Majid Jahanshahi, Ehsan Ziaei, Ali Salami, Khatere Mokhtari, Koorosh Shahpasand, Najma Farahani, Tohid Emami Meybodi, Maliheh Entezari, Afshin Taheriazam, Kiavash Hushmandi, Mehrdad Hashemi","doi":"10.1186/s12943-025-02267-0","DOIUrl":"https://doi.org/10.1186/s12943-025-02267-0","url":null,"abstract":"Glioblastoma multiforme (GBM) is the most prevalent and aggressive primary brain tumor in adults, characterized by a poor prognosis and significant resistance to existing treatments. Despite progress in therapeutic strategies, the median overall survival remains approximately 15 months. A hallmark of GBM is its intricate molecular profile, driven by disruptions in multiple signaling pathways, including PI3K/AKT/mTOR, Wnt, NF-κB, and TGF-β, critical to tumor growth, invasion, and treatment resistance. This review examines the epidemiology, molecular mechanisms, and therapeutic prospects of targeting these pathways in GBM, highlighting recent insights into pathway interactions and discovering new therapeutic targets to improve patient outcomes.\u0000","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"32 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Traditional Chinese medicine in lung cancer treatment
IF 37.3 1区 医学
Molecular Cancer Pub Date : 2025-02-26 DOI: 10.1186/s12943-025-02245-6
Zhichao Xi, Rongchen Dai, Yufei Ze, Xue Jiang, Mengfan Liu, Hongxi Xu
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