Translational Oncology最新文献

{"title":"Exploring the role of the oral microbiome in saliva, sputum, bronchoalveolar fluid, and lung cancer tumor tissue: A systematic review","authors":"Adrianna Michalina Kwiatkowska ,&nbsp;Jaime Andrés Guzmán ,&nbsp;Gloria Inés Lafaurie ,&nbsp;Diana Marcela Castillo ,&nbsp;Andrés F. Cardona","doi":"10.1016/j.tranon.2025.102557","DOIUrl":"10.1016/j.tranon.2025.102557","url":null,"abstract":"<div><h3>Objective</h3><div>To explore the association between the oral microbiome and the presence or progression of lung cancer (LC) using metagenomic sequencing techniques.</div></div><div><h3>Methods</h3><div>Databases, including PubMed and EMBASE, were reviewed. Eligible studies included the study of oral microorganisms via genomic sequencing and molecular mechanisms associated with LC in saliva, sputum, bronchoalveolar lavage fluid (BALF), or tumor tissue from LC patients. A quality analysis of the studies was carried out, and a qualitative synthesis was performed according to the localization and sample type. Meta-analysis was performed on alpha diversity indexes.</div></div><div><h3>Results</h3><div>Of the 1880 scrutinized articles, 50 studies were selected, comprising 29 cross-sectional, 7 case-control, and 14 cohort studies. The quality analysis sheds light on potential biases. The findings revealed a conspicuous overgrowth of specific microbial taxa in LC patients' saliva BALF samples of <em>Veillonella</em> and <em>Streptococcus</em>. Conversely, the <em>Bacteroides</em> genus, related to periodontal disease, exhibited no significant correlation with LC. Microorganisms in tumoral tissue were associated with poor prognosis. <em>Veillonella</em> was associated with a better response to ICIs therapy. Oral microorganisms were related to metabolic reprogramming with xenobiotic biodegradation, amino acid, sugar, sucrose, and lipidic metabolism, immune modulation, and proinflammatory responses.</div></div><div><h3>Conclusion</h3><div>Overgrowth of specific oral microorganisms in the saliva and BALF is associated with diagnosis, poor prognosis, and low response to immunotherapy. <em>Veillonella</em> could be a marker for response to ICIs therapy. Further well-designed studies should evaluate the impact of the oral microbiome on the response to ICIs.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"62 ","pages":"Article 102557"},"PeriodicalIF":5.0,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145222572","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":"A central research portal for mining pancreatic clinical and molecular datasets and accessing biobanked samples","authors":"Jorge Oscanoa ,&nbsp;Helen Ross-Adams ,&nbsp;Abu Z.M. Dayem Ullah ,&nbsp;Trupti S. Kolvekar ,&nbsp;Lavanya Sivapalan ,&nbsp;Emanuela Gadaleta ,&nbsp;Graeme J. Thorn ,&nbsp;Maryam Abdollahyan ,&nbsp;Ahmet Imrali ,&nbsp;Amina Saad ,&nbsp;Rhiannon Roberts ,&nbsp;Christine S. Hughes ,&nbsp;PCRFTB, Hemant M. Kocher ,&nbsp;Claude Chelala","doi":"10.1016/j.tranon.2025.102550","DOIUrl":"10.1016/j.tranon.2025.102550","url":null,"abstract":"<div><h3>Objectives</h3><div>We present Pancreas Genome Phenome Atlas (PGPA) as a resource for the mining and analysis of pancreatic -omics datasets, and demonstrate the biological interpretations possible due to this dynamic analytics hub accommodating an extensive range of publicly available datasets.</div></div><div><h3>Methods</h3><div>Clinical and molecular datasets from four primary sources are included (The Cancer Genome Atlas, International Cancer Genome Consortium, Cancer Cell Line Encyclopaedia, Genomics Evidence Neoplasia Information Exchange), which form the foundation of -omics profiling of pancreatic malignancies and related lesions (<em>n</em> = 7760 specimens). Several user-friendly analytical tools to integrate and explore molecular data derived from these primary specimens and cell lines are available. Crucially, PGPA is positioned as the data access point for Pancreatic Cancer Research Fund Tissue Bank – the only national pancreatic cancer biobank in the UK. This will pioneer a new era of biobanking to promote collaborative studies and effective sharing of multi-modal molecular, histopathology and imaging data (&gt;125 000 specimens from &gt;3980 cases and controls; &gt;2700 radiology images, and &gt;2630 digitised H&amp;Es from 401 donors) to accelerate validation of <em>in silico</em> findings in patient-derived material.</div></div><div><h3>Results</h3><div>We demonstrate the practical utility of PGPA by investigating somatic variants associated with established transcriptomic subtypes and disease prognosis: several patient-specific variants are clinically actionable and may be leveraged for precision medicine.</div></div><div><h3>Conclusions</h3><div>This places PGPA at the analytical forefront of pancreatic biomarker-based research, providing the user community with a distinct resource to facilitate hypothesis-testing on public data, validate novel research findings, and access curated, high-quality patient tissues for translational research.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"62 ","pages":"Article 102550"},"PeriodicalIF":5.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145222571","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":"Penfluridol enhances anti-tumor immunity in colorectal cancer by inducing proteasome-mediated degradation of PD-L1 via the activation of AMPK","authors":"Jianling Wang ,&nbsp;Yan Zhang ,&nbsp;Quan Chen ,&nbsp;Xiaorui Wang ,&nbsp;Rongrong Cui ,&nbsp;Peng Hou","doi":"10.1016/j.tranon.2025.102559","DOIUrl":"10.1016/j.tranon.2025.102559","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is a prevalent and aggressive malignancy globally, and immune checkpoint inhibitors targeting the PD-1/PD-L1 axis have become one of the effective strategies for the treatment of this disease. Here, we discovered penfluridol (PFD), an antipsychotic drug, as a novel modulator of this immune checkpoint pathway. Firstly, we confirmed anti-tumor efficacy of PFD in CRC cells by a series of <em>in vitro</em> experiments. Next, we found that PFD promoted the ubiquitin-proteasome-mediated degradation of PD-L1 to reduce PD-L1 expression on cell surface, thereby enhancing the killing effect of T cells on cancer cells. Further mechanistic investigations revealed that PFD activated AMP-activated protein kinase (AMPK) to facilitate PD-L1 degradation. Also, we demonstrated that PFD had a synergistic anti-tumor effect with PD-1 antibodies using MC38 tumor-bearing mouse model. Compared with monotherapy, combined therapy of PFD and PD-1 antibodies caused a pronounced improvement in anti-tumor immune responses by boosting the infiltration of both CD8+ and CD4+ <em>T</em> cells, with an excellent biosafety. Thus, our findings offer compelling evidence to support the anti-tumor and immunomodulatory roles of PFD in CRC, highlighting the potential of repurposing PFD in improving anti-tumor response to immune checkpoint blockades (ICBs).</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"62 ","pages":"Article 102559"},"PeriodicalIF":5.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145222567","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":"CD70-targeted CAR-T/NK therapy: Rationale, advances, and future directions","authors":"Sijia Yan,&nbsp;Xiaojian Zhu,&nbsp;Yi Xiao","doi":"10.1016/j.tranon.2025.102555","DOIUrl":"10.1016/j.tranon.2025.102555","url":null,"abstract":"<div><div>Chimeric antigen receptor T and natural killer (CAR-T/NK) cells is a rapidly evolving cellular immunotherapy technology that has made great achievements in the treatment of hematologic diseases. CD70, as a surface antigen expressed on tumor cells in a variety of hematologic malignancies, including acute myeloid leukemia, non-Hodgkin lymphoma, multiple myeloma, etc., and solid tumors such as renal cell carcinoma, osteosarcoma, and glioma, is a potential target for CAR-T/NK cells. Several preclinical studies and clinical trials on CAR-T/NK cells targeting CD70 are currently underway, bringing new hope for the treatment of CD70-positive tumors.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"62 ","pages":"Article 102555"},"PeriodicalIF":5.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145222492","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":"A scheme to navigate “biomolecule X” from Platycladi Folium against hepatocellular carcinoma via phytoinformatics","authors":"Ki-Kwang Oh,&nbsp;Seol Hee Song,&nbsp;Jeong Ha Park,&nbsp;Min Ju Kim,&nbsp;Dong Joon Kim,&nbsp;Ki-Tae Suk","doi":"10.1016/j.tranon.2025.102546","DOIUrl":"10.1016/j.tranon.2025.102546","url":null,"abstract":"<div><h3>Background</h3><div><em>Platycladi Folium</em> (PF) is a natural herbal plant and a significant resource with anti-cancer agents, including hepatocellular carcinoma (HCC). In this study, we applied a phytoinformatics approach to identify potential therapeutic components for HCC treatment.</div></div><div><h3>Methods</h3><div>The target(s) of PF-derived molecules detected by gas chromatography-mass spectrometry (GC–MS) were relieved from reliable public bioinformatics databases (Similarity Ensemble Approach; SEA, and Swiss Target Prediction; STP), and HCC-responding targets were identified through human disease databases (DisGeNET, and OMIM databases). Holistically, PF-molecules-targets-mechanisms (PMTM) network was constructed to elucidate their therapeutic relationships. Next, molecular docking test (MDT) was conducted to obtain key molecule(s) on key target(s) in a key mechanism. The chemical reactivity level of the key molecule(s) was determined with density functional theory (DFT). Moreover, the toxicity of key molecule(s) was assessed using <em>in silico</em> platform.</div></div><div><h3>Results</h3><div>Ultimately, the 27 final targets were considered as significant targets, revealing in PPI network, then, ESR1 was a key modulator in the network. MDT revealed that 5A-Androstan-3B,17B-diol, 17A-methyl was bound most stably to ESR1, ESR2, FGF1, and Kaurenoic acid formed the most stable conformers with SHH, RXRA, RARA, and RARB. Then, Humulene had the strongest affinity on GLI1, and GLI2. The three molecules showed effective chemical reactivity in density functional theory (DFT), in parallel, they had no noticeable toxicity to develop as new agents.</div></div><div><h3>Conclusions</h3><div>Overall, our findings indicate that three biomolecules (5A-Androstan-3B,17B-diol, 17A-methyl; Kaurenoic acid; and Humulene) from PF have the potential to exert therapeutic effects on multiple targets in the ‘Pathways in Cancer’ pathway.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"62 ","pages":"Article 102546"},"PeriodicalIF":5.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145222491","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":"HDAC inhibitor (SAHA) enhances B7-H3-specific CAR T cell cytotoxic efficacy against chondrosarcoma cells and prolongs survival in an orthotopic mouse model","authors":"David O. Osei-Hwedieh ,&nbsp;Lile He ,&nbsp;Kun Wang ,&nbsp;Song Fan ,&nbsp;Soldano Ferrone ,&nbsp;Xinhui Wang ,&nbsp;Joseph H. Schwab","doi":"10.1016/j.tranon.2025.102538","DOIUrl":"10.1016/j.tranon.2025.102538","url":null,"abstract":"<div><div>High-grade Chondrosarcoma (Grades II, III, and dedifferentiated) is an aggressive primary malignant bone tumor characterized by hyaline cartilaginous neoplastic tissue without any effective systemic therapy. Localized disease is treated with a complete surgical resection with negative margins. However, high-grade chondrosarcoma often spreads systemically, leading to low overall survival rates of 29 %. These clinical findings emphasize the urgent need for improved systemic therapies. Among them is chimeric antigen receptor (CAR) T cell therapy. In this study, tumor-associated antigen B7-H3, which is highly expressed in chondrosarcoma cells but has a restricted expression in normal tissues, is targeted with B7-H3-specific CAR T cells. Our results show that these CAR T cells are effective in killing chondrosarcoma cells <em>in vitro and</em> retard chondrosarcoma tumor growth in immunodeficient mice, which resulted in prolonged survival of tumor-bearing mice. To enhance the antitumor activity of B7-H3 CAR T cells, tumor cells or CAR T cells were treated <em>ex-vivo</em> with a low dose of vorinostat (SAHA), a histone deacetylase (HDAC) inhibitor that upregulates B7-H3 transcription and expression in several types of solid cancer cells as well as the chimeric antigen receptor. Our results demonstrate that treatment of B7-H3 CAR T cells or chondrosarcoma cells with SAHA enhances CAR T cell antitumor cytotoxic activity <em>in vitro</em> and <em>in vivo</em>.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"62 ","pages":"Article 102538"},"PeriodicalIF":5.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213838","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":"Selective antitumor activity of Tumor Treating Fields (TTFields) involving molecular factors in cancer cells and tumor microenvironment","authors":"Ilaria Fuso Nerini ,&nbsp;Rosy Amodeo ,&nbsp;Maurizio D’Incalci ,&nbsp;Monica Lupi","doi":"10.1016/j.tranon.2025.102556","DOIUrl":"10.1016/j.tranon.2025.102556","url":null,"abstract":"<div><div>The local application of low-intensity electric fields at intermediate frequencies (Tumor Treating Fields – TTFields) has emerged as an effective anticancer treatment in conjunction with chemotherapy and immunotherapy for several solid tumors. Despite this progress, the phenotypic and genetic determinants underlying tumor sensitivity to TTFields remain largely unexplored, representing a critical gap in our understanding.</div><div>This review provides a comprehensive analysis of preclinical and translational studies describing the cellular factors that influence the anticancer properties of TTFields. An overview of recent omics studies on the complex cellular and molecular processes initiated by TTFields has revealed important mechanisms of action that warrant further investigation for their therapeutic potential.</div><div>The goal is to identify effects that can be leveraged to develop rational, synergistic co-treatments with anticancer agents that have complementary modes of action. In particular, the ability of TTFields to modulate the tumor microenvironment and reverse the local and systemic immunosuppression could represent a promising strategy to enhance the efficacy of immunotherapy across different tumor types.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"62 ","pages":"Article 102556"},"PeriodicalIF":5.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207641","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":"USP11 is involved in the sensitivity of liver cancer cells to ferroptosis and taxanes through the regulation of NRF2 ubiquitin-mediated degradation","authors":"Shujia Kong ,&nbsp;Chen Zhao ,&nbsp;Jiaxun Li ,&nbsp;Xin Pan ,&nbsp;Yanwen Li","doi":"10.1016/j.tranon.2025.102553","DOIUrl":"10.1016/j.tranon.2025.102553","url":null,"abstract":"<div><h3>Background</h3><div>Ubiquitin-specific protease 11 (USP11) plays a significant role in tumor progression through various mechanisms. However, in hepatocellular carcinoma (HCC) research, the mechanism by which USP11 impacts ferroptosis and sensitivity to taxanes in HCC remains ambiguous. The aim of this study was to investigate the effects of USP11 on ferroptosis and sensitivity to taxanes in HCC.</div></div><div><h3>Methods</h3><div>Research was conducted on clinical HCC specimens, cell lines (THLE2, HepG2, SNU449, Huh7, and Hep3B), and subcutaneous tumorigenesis models. Gene and protein expression was detected using real-time quantitative polymerase chain reaction (RT‒qPCR), western blotting, and immunohistochemistry. Cell proliferation and migration were detected using cell counting kit-8 (CCK-8), colony, scratch, and Transwell assays. Ferroptosis was evaluated by Fe²⁺, glutathione (GSH), malondialdehyde (MDA) and reactive oxygen species (ROS)-related indices.</div></div><div><h3>Results</h3><div>USP11 was upregulated in HCC clinical tissues, and overexpression or knockdown of <em>USP11</em> promoted or inhibited the proliferation, migration and invasion of HCC cells <em>in vitro</em>, respectively. Furthermore, when triggered by erastin, overexpression of USP11 led to a reduction in Fe²⁺, MDA, and ROS levels in HepG2 and SNU449 cells but an increase in GSH, solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4), thus inhibiting ferroptosis in HCC cells. USP11 also inhibited the sensitivity of HCC cells to taxanes (paclitaxel, docetaxel, and cabazitaxel). From a mechanistic standpoint, USP11 enhanced nuclear factor erythroid-2-related factor 2 (NRF2) expression via deubiquitination, thus reducing ferroptosis and taxane sensitivity in HCC cells.</div></div><div><h3>Conclusion</h3><div>This research highlights the crucial role of USP11 in ferroptosis and drug resistance in HCC, identifying a new potential target for the treatment of HCC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"62 ","pages":"Article 102553"},"PeriodicalIF":5.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207669","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 non-coding RNAs in pleural mesothelioma","authors":"Giulia Tonnini ,&nbsp;Giulia Di Mauro ,&nbsp;Maria Letizia Tramarin ,&nbsp;Anna Meneghetti ,&nbsp;Ilaria Bononi ,&nbsp;Chiara Mazziotta ,&nbsp;John Charles Rotondo ,&nbsp;Elisa Mazzoni ,&nbsp;Maria Rosa Iaquinta ,&nbsp;Elisabetta Trabetti ,&nbsp;Cristina Bombieri ,&nbsp;Monica De Mattei ,&nbsp;Mauro Tognon ,&nbsp;Fernanda Martini","doi":"10.1016/j.tranon.2025.102547","DOIUrl":"10.1016/j.tranon.2025.102547","url":null,"abstract":"<div><h3>Background</h3><div>Pleural mesothelioma (PM) is a rare and highly aggressive tumor, primarily caused by asbestos exposure. Its long latency period and late-stage diagnosis severely limit therapeutic options.</div></div><div><h3>Aim</h3><div>Recent evidence suggests that non-coding RNAs (ncRNAs)—including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs)—play key roles in PM biology. This review aims to synthesize current knowledge on ncRNA dysregulation in PM and explore their diagnostic, prognostic, and therapeutic potential.</div></div><div><h3>Scope</h3><div>We summarize studies addressing the expression and function of ncRNAs in tumors and in circulating biofluids of PM patients. Particular attention is given to how ncRNAs regulate proliferation, apoptosis, and migration, and how competing endogenous RNA (ceRNA) networks shape gene regulation in PM.</div></div><div><h3>Novelty and Conclusion</h3><div>Unlike previous reviews, this work integrates findings across different classes of ncRNAs and their interactions, highlighting the emerging concept of ceRNA networks in PM. By bridging molecular mechanisms with potential clinical applications, we provide an updated and comprehensive framework that may inform future strategies for diagnosis, prognosis, and targeted therapy in PM.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"62 ","pages":"Article 102547"},"PeriodicalIF":5.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145201420","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":"HDAC2 promotes malignant progression by the RBM47/NONO axis in medulloblastoma","authors":"Houji Song ,&nbsp;Siyu Zhang ,&nbsp;Jie Chen ,&nbsp;Gaichao Zhao ,&nbsp;Fujing Wei ,&nbsp;Jingjie Zhou ,&nbsp;Tianxiang Feng ,&nbsp;Hui Zhao ,&nbsp;Ping Liang ,&nbsp;Hongjuan Cui","doi":"10.1016/j.tranon.2025.102549","DOIUrl":"10.1016/j.tranon.2025.102549","url":null,"abstract":"<div><h3>Background</h3><div>Medulloblastoma (MB) is one of the most prevalent pediatric brain tumors, constituting approximately 20 % of all childhood brain malignancies. The modification of histone acetylation is recognized for its significance in tumor growth and survival. However, its role in MB has been scarcely investigated. Here, we demonstrate that the Histone deacetylase 2 (HDAC2) modulates oncogene expression and promotes tumorigenesis in MB tumors.</div></div><div><h3>Methods</h3><div>To elucidate the biological roles of HDAC2 in MB, we employed lentivirus-mediated RNA interference (RNAi) to deplete HDAC2. Subsequently, we employed EdU, flow cytometry (FCM), Transwell assay, and cell line-derived xenograft (CDX) models to evaluate the effects of HDAC2 on proliferation, migration and invasion of MB cells. The underlying mechanism of HDAC2 in MB was further investigated using qRT-PCR, Western blot, CHIP-qPCR, and Luciferase reporter assays.</div></div><div><h3>Results</h3><div>We found that HDAC2 is overexpressed in both MB patient tissues and MB cell lines. The knockdown of HDAC2 significantly inhibited the proliferation, migration, and invasion abilities of MB cells. Mechanistically, HDAC2 promoted RBM47 expression through H3K27 deacetylation. The expression of NONO was increased in MB cells overexpressing RBM47. Critically, HDAC2 knockdown enhanced the sensitivity of MB cells to temozolomide treatment.</div></div><div><h3>Conclusions</h3><div>Our results suggest that HDAC2 plays an oncogenic role in MB. Targeting the HDAC2/RBM47/NONO axis could be a potential therapeutic strategy for MB patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"62 ","pages":"Article 102549"},"PeriodicalIF":5.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145201438","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}