Cancer Cell International最新文献

{"title":"Plumbagin targets the GLUT1/MMP-2 axis to inhibit oral squamous cell carcinoma progression.","authors":"Fei He, Weiqi Wang, Sadam Ahmed Elayah, Linyang Xie, Ming Yu, Yuxin Gong, Hao Cui, Xiang Liang, Junbo Tu, Ying Han, Sijia Na","doi":"10.1186/s12935-025-03915-7","DOIUrl":"10.1186/s12935-025-03915-7","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to investigate the clinicopathological characteristics and prognostic value of GLUT1 in oral squamous cell carcinoma (OSCC) and the effect of plumbagin (PLB) on inhibiting OSCC invasion and metastasis through the GLUT1/Matrix Metalloproteinase 2 (MMP2) axis pathway.</p><p><strong>Materials and methods: </strong>One hundred and twenty human OSCC specimens were collected. Immunohistochemistry was performed to analyze the expression, clinicopathological characteristics, and prognostic value of GLUT1 in these specimens. Cal27 and SCC9 cell lines were used to investigate the role of PLB in cell proliferation, migration, invasion, and metastasis in vitro and in vivo.</p><p><strong>Results: </strong>Immunohistochemistry showed significant associations between GLUT1 expression and MMP2, tumor recurrence, lymphatic metastasis, and TNM stage. In vitro and in vivo experiments demonstrated that PLB inhibited OSCC cell proliferation, migration, and invasion by downregulating GLUT1 and MMP2. WZB117, a GLUT1 inhibitor, also reduced cell colony formation, migration, and invasion. However, univariate and multivariate analyses indicated that GLUT1 expression was not an independent prognostic marker for OSCC overall and disease-free survival.</p><p><strong>Conclusions: </strong>The findings demonstrated a novel anti-cancer mechanism of plumbagin, inhibiting OSCC invasion and migration by suppressing the GLUT1/MMP2 axis pathway, providing a theoretical basis for the future clinical use of plumbagin in the treatment of OSCC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"283"},"PeriodicalIF":6.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728096","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":"Cyclin dependent kinase 9 inhibitor induces transcription-replication conflicts and DNA damage accumulation in breast cancer.","authors":"Minyoung Lee, Kyung-Hun Lee, Ahrum Min, So Hyeon Kim, Sujin Ham, Hae Min Hwang, Youlim Noh, Yu-Jin Kim, Dae-Won Lee, Jiwon Koh, Seock-Ah Im","doi":"10.1186/s12935-025-03897-6","DOIUrl":"10.1186/s12935-025-03897-6","url":null,"abstract":"<p><strong>Background: </strong>Cyclin-dependent kinase 9 (CDK9) is a crucial regulator of transcriptional progression of RNA polymerase-II (RNAP2). RNA polymerases trapped in DNA can be a source of transcription-replication conflict (T-R conflict), which is a common source of replication stress. AZD4573, a highly selective CDK9 inhibitor, has been shown to induce apoptosis in leukemia cell lines, while its anti-tumor potential in breast cancer has yet to be elucidated.</p><p><strong>Methods: </strong>To evaluate the cytotoxicity of AZD4573 in vitro, MTT assays were performed. The expression of signal transduction molecules was determined using Western blotting, immunoprecipitation, and immunofluorescence. Apoptotic cell death was verified by the annexin-V assay. DNA strand breaks and repair efficacy were evaluated through the alkaline comet assay. The siRNA knock-down system was used to confirm the action mechanism.</p><p><strong>Results: </strong>AZD4573 induced T-R conflicts during S-phase, increasing replication stress and DNA strand breaks, resulting in apoptosis by induction of caspase-3. Furthermore, we identified Dead-box 25 (DDX25) helicase as a key mediator in resolving the T-R conflicts. Nuclear translocation of DDX25 correlated with reduced sensitivity to AZD4573 by the resolution of T-R conflicts.</p><p><strong>Conclusions: </strong>Inhibition of CDK9 by AZD4573 induces the accumulation of DNA damage through T-R conflicts. DDX25 helicases were identified as a key mediator in resolving T-R conflicts and the reduced sensitivity to AZD4573.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"282"},"PeriodicalIF":6.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717596","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":"Synthesis of 5-Fluorouracil (5-FU) coated platinum nanoparticles and apoptotic effects on U87 human glioblastoma cells.","authors":"Atena Abed, Merat Karimi, Majid Nejati, Michael R Hamblin, Seyed Abbas Mirzaei, Mostafa Sarvizadeh, Hamed Mirzaei","doi":"10.1186/s12935-025-03893-w","DOIUrl":"10.1186/s12935-025-03893-w","url":null,"abstract":"<p><strong>Background: </strong>5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent; however, its clinical application is often limited by systemic toxicity and the development of drug resistance. To enhance its therapeutic efficacy, novel drug delivery strategies are under investigation. This study evaluated the use of platinum nanoparticles (PtNPs) as a nanocarrier system for 5-FU delivery to glioblastoma cells, focusing on their effects on apoptosis-related proteins.</p><p><strong>Methods: </strong>The binding affinity and interactions of 5-FU with key apoptotic proteins (BAX, Bcl2, and Caspase-3) were assessed using molecular docking and validated through molecular dynamics (MD) simulations. PtNPs were synthesized and characterized via scanning electron microscopy (SEM), X-ray diffraction (XRD), and dynamic light scattering (DLS). Drug loading and encapsulation efficiency were determined, and cytotoxicity assays were conducted in U87 glioblastoma cells. The expression levels of apoptosis-related genes and proteins were evaluated to determine the biological impact of the formulations.</p><p><strong>Results: </strong>Docking results confirmed effective binding of 5-FU to Bcl2, Caspase-3, and BAX, with MD simulations supporting stable complex formation, particularly with Bcl2 and Caspase-3. The synthesized PtNPs exhibited favorable physicochemical properties, including uniform morphology and high drug loading efficiency. In vitro release studies revealed a sustained release profile for the PtNPs/5-FU formulation. Furthermore, PtNPs/5-FU significantly downregulated the expression of EMT- and proliferation-related genes (cyclin D1, ZEB1, and Twist) and suppressed Bcl2 protein levels, resulting in enhanced apoptosis in U87 cells.</p><p><strong>Conclusion: </strong>PtNPs effectively functioned as a delivery platform for 5-FU, improving its release kinetics and promoting apoptotic responses while potentially minimizing systemic toxicity. These findings support further exploration of PtNP-based drug delivery systems as a promising strategy for glioblastoma treatment.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"280"},"PeriodicalIF":6.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717599","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":"DNAJC24 suppresses breast cancer malignancy and serves as a prognostic biomarker.","authors":"Wenjing Meng, Wei Liu, Yulong Yang, Xiaorui Wang, Linlin Zhan, Yi Luo, Liwei Chen, Yu Wang, Guangtao Li, Yehui Shi, Yuchao He, Zhongsheng Tong, Hua Guo","doi":"10.1186/s12935-025-03918-4","DOIUrl":"10.1186/s12935-025-03918-4","url":null,"abstract":"<p><strong>Background: </strong>Based on the current markers, numerous targeted therapies have been put forward for clinical application; however, treatment resistance and recurrence still remain the main causes of breast cancer-related mortality. In addition, breast cancer exhibits significant heterogeneity, and patients with apparently similar tumor subtypes exhibit variable responses to identical drug treatments. Therefore, accurate prediction of breast cancer progression and personalized treatment plans will maximize patient benefit by avoiding overtreatment and undertreatment.</p><p><strong>Methods: </strong>In this study, our emphasis was placed on exploring the function of DnaJ heat shock protein family member C24 (DNAJC24, also known as DPH4) in breast cancer through bioinformatic analysis by using public databases and clinicopathological samples. We performed in vitro functional assays to explore the biological roles of DNAJC24.</p><p><strong>Results: </strong>Bioinformatics analysis of TCGA data demonstrated significantly lower DNAJC24 expression in breast cancer tissues compared to adjacent paracancer tissues (p < 0.001). Immunohistochemistry showed low DNAJC24 expression in 72.4% (210/290) of breast cancer tissues versus 50.8% (134/264) of adjacent paracancer tissues. DNAJC24 expression decreased progressively with advanced clinical stages (p < 0.05), was lowest in HER2-enriched subtype, and highest in Luminal-A subtype. Overexpression of DNAJC24 in breast cancer cells significantly reduced colony formation (p < 0.05), proliferation rates, chemotaxis (p < 0.05), invasion (p < 0.05), and migration abilities (p < 0.05) compared to controls. Conversely, DNAJC24 knockdown in cancer cells produced opposite effects, significantly enhancing chemotaxis, invasion, and migration (all p < 0.05).</p><p><strong>Conclusions: </strong>Lower DNAJC24 expression is strongly associated with breast cancer malignancy, advanced clinical stages, aggressive molecular subtypes, and poorer prognosis. Functionally, DNAJC24 inhibits proliferation, invasion, and migration of breast cancer cells, underscoring its potential as a prognostic biomarker in breast cancer.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"279"},"PeriodicalIF":6.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717597","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":"Dual targeting of VEGFR2 and CSF1R with SYHA1813 confers novel strategy for treating both BRAF wild-type and mutant melanoma.","authors":"Wenhao Shi, Haotian Tang, Linjiang Tong, Peiran Song, Yuqing Huang, Zhipeng Wan, Gege Huang, Qiupei Liu, Zhengsheng Zhan, Yu Zhou, Yuantong Li, Jiaxin Wen, Bencan Tang, Wenhu Duan, Jian Ding, Xiaorui Li, Hua Xie","doi":"10.1186/s12935-025-03902-y","DOIUrl":"10.1186/s12935-025-03902-y","url":null,"abstract":"<p><strong>Background: </strong>Melanoma is notorious for its aggressive growth, metastatic spread, and heterogeneous response to therapy across BRAF (B-Raf proto-oncogene, serine/threonine kinase) genotypes. While BRAF inhibitors improve outcomes in V600E-mutant tumors, their benefit is limited in wild-type melanomas and by transient responses in mutant disease. Vascular endothelial growth factor receptor 2 (VEGFR2) driven angiogenesis and colony-stimulating factor-1 receptor (CSF1R) mediated immunosuppression each sculpt a permissive tumor microenvironment. We hypothesized that simultaneous blockade of both axes with SYHA1813, which currently undergoing Phase II clinical trials in China for solid tumor treatment, would yield a broadly applicable, microenvironment-targeted strategy for melanoma treatment.</p><p><strong>Methods: </strong>Subcutaneous xenograft models of BRAF wild-type (MeWo) and BRAF V600E-mutant (A375) melanoma were established (NOD-SCID mice), alongside an intracardiac metastasis model (Nude mice) using GFP-Luc-labeled A375 cells. SYHA1813 (2.5 mg/kg or 5 mg/kg), alone or combined with vemurafenib (20 mg/kg), was administered to assess tumor growth, metastatic burden, and microenvironmental modulation. Tumor growth inhibition rates and synergistic effects were quantified. The markers of angiogenesis, macrophage polarization and cell proliferation were analyzed via immunohistochemistry.</p><p><strong>Results: </strong>SYHA1813 monotherapy exhibited significant antitumor efficacy in BRAF wild-type MeWo and BRAF V600E-mutant A375 melanoma xenograft models at 5 mg/kg, achieving 72.5% and 79.8% tumor growth inhibition, respectively, surpassing vemurafenib in BRAF wild-type tumors. Treatment regimens were well tolerated, with no significant body weight changes observed. Mechanistically, SYHA1813 suppressed angiogenesis, attenuated M2 macrophage infiltration, and inhibited tumor cell proliferation as marked by reduced CD31, CD105, F4/80, CD206 and Ki67 expression. Moreover, we evaluated the combination of SYHA1813 with vemurafenib in BRAF V600E-mutant models and found that 2.5 mg/kg SYHA1813 treatment synergized with vemurafenib, enhancing tumor suppression to 72.9% inhibition compared to each monotherapy (38.9% and 34.7%, respectively). Furthermore, we established a systemic intracardiac metastasis mouse model to assess the impact of SYHA1813 on melanoma metastasis. The results showed that SYHA1813 reduced systemic metastasis by 76.6%, significantly curtailing brain and bone metastases.</p><p><strong>Conclusions: </strong>Dual targeting of VEGFR2 and CSF1R with SYHA1813 confers a novel microenvironmentcentric strategy for treating both BRAF wildtype and mutant melanoma. By concurrently disrupting angiogenesis and macrophagemediated immunosuppression, SYHA1813 demonstrates strong therapeutic and antimetastatic activity to melanoma, warranting further clinical development as monotherapy or in combination with BRAF V600E inhibitors.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"281"},"PeriodicalIF":6.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717598","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":"TMEM16A in prostate cancer: mechanistic insights and therapeutic implications.","authors":"Jia Wei He, Pei Zhen Li, Zi Xuan Huang","doi":"10.1186/s12935-025-03914-8","DOIUrl":"10.1186/s12935-025-03914-8","url":null,"abstract":"<p><p>Transmembrane protein 16A (TMEM16A), functions as a calcium-activated chloride channel and has been recognized as a crucial factor in the pathophysiological processes of prostate cancer. Its elevated expression in metastatic prostate cancer cell lines is associated with unfavorable clinical outcomes, indicating its potential use as both a biomarker and a therapeutic target. This review emphasizes TMEM16A's involvement in facilitating cancer cell proliferation, migration, and invasion via various signaling cascades, notably the MAPK pathway. The inhibition of TMEM16A has yielded encouraging results in preclinical studies, highlighting its promise as a target for innovative therapeutic approaches. Additionally, examining TMEM16A's involvement in benign prostatic hyperplasia (BPH) enhances our comprehension of its relevance to prostatic health. Future investigations should focus on clarifying the fundamental mechanisms underlying TMEM16A's role and assessing its clinical applicability across various cancer types.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"278"},"PeriodicalIF":6.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706416","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":"Identification of novel biomarkers involved in oral squamous cell carcinoma by whole transcriptome sequencing and bioinformatics analysis.","authors":"Hongliang Du, Zhenze Wang, Mengyi Qi, Yunqing Pang, Qingling Lin, Dengqi He, Jing Wang","doi":"10.1186/s12935-025-03913-9","DOIUrl":"10.1186/s12935-025-03913-9","url":null,"abstract":"<p><strong>Background: </strong>Oral squamous cell carcinoma (OSCC) is among the most common malignant tumors in the oral and maxillofacial regions, characterized by high drug resistance and poor treatment outcomes. This underscores the urgent need to identify novel biomarkers for OSCC.</p><p><strong>Methods: </strong>Differentially expressed messenger RNAs (mRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) (DE-mRNAs, DE-miRNAs, and DE-lncRNAs) between primary and control groups, as well as metastatic and primary groups, were identified using whole transcriptome sequencing data. Candidate OSCC genes were derived from DE-mRNAs. Potential biomarkers were then identified using five algorithms from CytoHubba. Biomarkers were validated via univariate Cox regression and Kaplan-Meier (K-M) survival analysis. Additional analyses included subcellular localization, mutation analysis, and Gene Set Enrichment Analysis (GSEA). Key drugs for OSCC treatment were also identified. Quantitative real time polymerase chain reaction (qRT-PCR) and immunohistochemistry were employed to verify the expression levels of key biomarkers.</p><p><strong>Results: </strong>A total of 304 candidate genes were identified, with 29 potential biomarkers selected by five algorithms. ANPEP, APOB, GLP1R, and SI exhibited significant survival differences in the K-M curves, establishing them as OSCC biomarkers. These biomarkers were predominantly localized in the cytoplasm, with SI and APOB showing the highest mutation susceptibility. Enrichment analysis revealed that the 'interferon-gamma response'biological function was co-enriched by ANPEP, APOB, and SI. Furthermore, BIBW2992 (afatinib) and PF.02341066 (crizotinib) were most strongly correlated with the biomarkers, suggesting their potential as key drugs for OSCC treatment. Additionally, the findings were validated by qRT-PCR and immunohistochemical analyses, and the results were consistent with the RNA-seq data.</p><p><strong>Conclusion: </strong>ANPEP, APOB, GLP1R, and SI were identified as potential OSCC biomarkers, offering valuable insights for further research and therapeutic development.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"277"},"PeriodicalIF":6.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688980","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":"Revolutionizing cancer treatment: engineering mesenchymal stem cell-derived small extracellular vesicles.","authors":"Ameneh Shokati, Mahshid Akhavan Rahnama, Ladan Jalali, Saghar Hoseinzadeh, Saman Masoudifar, Mohammad Ahmadvand","doi":"10.1186/s12935-025-03900-0","DOIUrl":"10.1186/s12935-025-03900-0","url":null,"abstract":"<p><p>In recent years, use of exosomes is one of the important approaches to treat cancer. Mesenchymal stem cells are multipotent stem cells which are very putative sources for modulating the immune system and importantly inhibiting immune responses against tumor cells. Small extracellular vesicles (small EVs) are extracted from mesenchymal stem cells can have therapeutic approaches for delivering targeted drugs to cancer cells and also tumors via regulation of signaling pathways.There are challenges in use of exosomes in cancer treatment which need to be improved. Engineering in small EVs can recover the role of exosomes such as drug delivery and therapeutic tools. There are preclinical and clinical studies in the field of mesenchymal stem cells derived from small EVs which demonstrates efficacy of these approaches in the field of cancer.In consideration of problems in large scale production and so on, engineered small EVs as treatment approaches for cancers, it is resulted that they retain most characteristics of cells which are derived from, are responsible for their immunomodulatory impacts driving positive changes in the tumor microenvironment.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"275"},"PeriodicalIF":5.3,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682067","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":"UCHL3: a crucial deubiquitinase in DNA damage repair and tumor progression.","authors":"Jiahao Liu, Shulu Hu, Junqi Xiao, Jumei Zhou","doi":"10.1186/s12935-025-03884-x","DOIUrl":"10.1186/s12935-025-03884-x","url":null,"abstract":"<p><p>Ubiquitin carboxyl terminal hydrolase L3 (UCHL3) is a deubiquitinase belonging to UCH protease family. Previous studies have demonstrated that abnormal expression of UCHL3 is correlated with the development of human diseases, especially in tumors. Notably, UCHL3 exhibits contradictory biological functions across different cancer types. Initial studies identified UCHL3 as a tumor suppressor in prostate cancer. However, emerging evidence suggests that UCHL3 serves as an oncogene in other cancers. Several UCHL3 inhibitors have shown a promising anti-tumor effect in vitro and in vivo. UCHL3 has also been linked to DNA damage repair, which is essential for genome stability. Overexpression of UCHL3 enhances DNA damage repair induced resistance to chemotherapy or radiotherapy in certain tumor types. This review aims to summarize the promoting role of UCHL3 in DNA damage repair and its dual, paradoxical roles in tumor progression, along with the associated mechanisms, and to provide insights into the use of UCHL3 as a therapeutic target for overcoming DNA damage repair-mediated resistance to chemotherapy and radiotherapy, as well as for treating tumors.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"276"},"PeriodicalIF":5.3,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682069","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":"Single cell sequencing deciphering the heterogeneous landscape of blastic plasmacytoid dendritic cell neoplasm with novel MYB-ZFAT fusion gene.","authors":"Ruijuan Li, Wenyong Kuang, Haixia Yang, Benshan Zhang, Kexin Zhao, Weiyi Fang, Zhao Cheng, Xianming Fu, Hongling Peng","doi":"10.1186/s12935-025-03899-4","DOIUrl":"10.1186/s12935-025-03899-4","url":null,"abstract":"<p><strong>Background: </strong>Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive blood cancer from plasmacytoid dendritic cell precursors. It's marked by CD4, CD56, CD123, and CD303/CD304 expression and involves molecular disruptions like chromatin deletions, mutations, and chromosomal translocations.</p><p><strong>Methods: </strong>The current study employed a comprehensive method with clinical samples, histology, FACS immunophenotyping, karyotype analysis, transcriptome and protein structure analysis, and single-cell sequencing to explore BPDCN's molecular basis.</p><p><strong>Results: </strong>The study discovered a new MYB-ZFAT gene fusion in a BPDCN patient and showed a diverse cell population, contradicting a single cell type theory. It found four major clusters (Cluster 1,2,3,8 ) and one cluster (clulster 12) with unique profiles and roles in disease progression. The research noted Key pathways include T cell receptor signaling, NK cell cytotoxicity, and hematopoiesis are involved in pathogenesis. The study emphasized MYB activation's role in BPDCN's cellular clustering and identity.</p><p><strong>Conclusion: </strong>The study indicates BPDCN's complexity with varied cellular origins and a significant role for MYB activation in its development. This research deepens our comprehension of BPDCN's pathogenesis and cell populations.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"274"},"PeriodicalIF":5.3,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682068","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}