Clinical and Experimental Medicine最新文献

{"title":"Circulating microRNAs as prognostic biomarkers in patients with oropharyngeal cancer undergoing radiotherapy: temporal dynamics analysis.","authors":"Bartłomiej Tomasik, Damian Mikulski, Bartosz Kamil Sobocki, Kasper Kuna, Anna Papis-Ubych, Konrad Stawiski, Jacek Burzyński, Jacek Fijuth, Piotr Kędzierawski, Jacek Sadowski, Rafał Stando, Robert Bibik, Łukasz Graczyk, Tomasz Latusek, Tomasz Rutkowski, Wojciech Fendler","doi":"10.1007/s10238-026-02237-w","DOIUrl":"https://doi.org/10.1007/s10238-026-02237-w","url":null,"abstract":"<p><p>The incidence of oropharyngeal cancer (OPC) is increasing. Thus, there is a need for biomarkers that can identify high-risk patients and support personalised treatment. This study investigated the prognostic significance of circulating microRNAs (miRNAs) for progression-free survival (PFS) and overall survival (OS) in patients with OPC undergoing radiotherapy (RT). The expression of 20 circulating miRNAs was analysed in serum samples collected both before and after RT as a possible prognostic marker in patients treated for OPC. We analysed 80 patients with OPC treated with curative-intent RT. The median PFS was 42.9 months (95%CI: 25.6 - not reached), and the median OS was 63.7 months (95%CI: 33.9 - not reached). In univariate analysis, higher pre-treatment levels of miR-21-5p (HR: 2.12, 95%CI: 1.34-3.36) and miR-148a-3p (HR: 1.38, 95%CI: 1.03-1.85), as well as lower post-treatment levels of miR-345-5p (HR: 0.61, 95%CI: 0.41-0.90), were associated with worse survival. These associations remained significant in multivariable analysis adjusted for clinical factors. A combined risk model based on pre-RT miR-21-5p and post-RT miR-345-5p identified a high-risk group with significantly shorter PFS (HR: 3.01, 95%CI: 1.27-7.14) and OS (HR: 3.19, 95%CI: 1.25-8.15) compared with the low-risk group. High pre-RT hsa-miR-21-5p and low post-RT hsa-miR-345-5p were both independently associated with inferior PFS and OS. These results support the clinical relevance of integrating dynamic miRNA profiling into risk-stratification frameworks and may potentially inform more personalised strategies for post-RT monitoring in OPC patients.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress on the regulation of mesothelioma driven by deubiquitinating enzyme BAP1.","authors":"Wan-Ting Xuan, Yao Dong, Si-Yuan Ma, Man Liu, Xiao-Qi Liu, Na-Na Yao, Lan-Xi Hu, Ling-Ling Shi, Lin Ma, Jing-Hui Bai, Bo Huang","doi":"10.1007/s10238-026-02249-6","DOIUrl":"https://doi.org/10.1007/s10238-026-02249-6","url":null,"abstract":"<p><p>Mesothelioma is a highly aggressive malignancy that develops through the combined influence of several factors, including environmental exposure, genetic susceptibility, immune status, and aberrant activation or dysregulation of signaling pathways. The BAP1 gene, a tumor suppressor located at chromosome 3p21.1, plays a pivotal role in maintaining genomic stability by functioning as a deubiquitinating enzyme in critical processes such as DNA damage repair, cell cycle regulation, and chromatin remodeling. Its proper activity requires nuclear localization via the nuclear localization signal (NLS) domain. When BAP1 undergoes a truncation mutation, the NLS loses its function and the protein is retained in the cytoplasm; whereas missense mutations in the UCH domain, whilst not necessarily altering subcellular localisation, can directly lead to the loss of deubiquitinase activity, thereby promoting tumour development.Consequently, elucidating the signaling pathways governed by BAP1, designing targeted therapeutic strategies for BAP1-mutant cancers, and implementing preventive interventions in BAP1 mutation carriers represent urgent clinical and research priorities.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary fatty acids intake and the risk of advanced cardiovascular-kidney-metabolic syndrome: evidence from NHANES 1999-2018.","authors":"Qiuhui Wang, Fengming Liang, Hongyang Xu, Yang Chen","doi":"10.1007/s10238-026-02251-y","DOIUrl":"https://doi.org/10.1007/s10238-026-02251-y","url":null,"abstract":"<p><p>Cardiovascular-Kidney-Metabolic syndrome (CKM) is a multisystem disorder involving cardiovascular, renal, and metabolic dysfunction, with advanced stages (3-4) linked to high morbidity and mortality. Dietary fatty acids (FA) play critical roles in lipid metabolism, insulin sensitivity, and inflammation, yet their associations with CKM progression remain unclear. Data were from National Health and Nutrition Examination Survey, with stages 3-4 defined as advanced CKM. Dietary intake of total fat acids (TFA), saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) was derived from two 24-h recalls and energy-adjusted using the residual method. Multivariable logistic regression and restricted cubic splines assessed associations between FA and advanced CKM. Sensitivity and subgroup analyses were also performed. Among 27,166 participants (median age: 55.0 years; 52.2% male), 6,634 were classified in advanced CKM stages (3-4). Multivariable logistic regression showed that higher intakes of TFA, SFA, and MUFA were significantly associated with advanced CKM. Compared with the lowest quartile, adjusted odds ratios in the highest quartile were 1.35 (95% CI: 1.05-1.40), 1.26 (95% CI: 1.09-1.37), 1.30 (95% CI: 1.10-1.55), and 1.26 (95% CI: 1.09-1.47), respectively. Restricted cubic spline analyses supported positive linear associations across all four fatty acid categories. Findings remained robust in sensitivity analyses excluding cancer patients, and consistent across key subgroups, with no significant interactions observed. Higher dietary intakes of TFA, SFA, MUFA, and PUFA were associated with greater odds of advanced CKM stages. These findings suggest that dietary fat quantity and composition may be important correlates of CKM severity and warrant further investigation in prospective studies.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis-associated immune modulation enhances temozolomide efficacy in experimental glioblastoma: potential implications for T-cell infiltration and tumour microenvironment dynamics.","authors":"Shaik Rahaman, Roli Kushwaha, Divya Vohora, Sumana Chakravarty, Ahmed Kamal","doi":"10.1007/s10238-026-02243-y","DOIUrl":"https://doi.org/10.1007/s10238-026-02243-y","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) remains a lethal and aggressive malignancy with limited response to standard therapies. This study hypothesized that artesunate, a ferroptosis inducer, enhances the cytotoxic and immunomodulatory efficacy of standard anticancer agents through mechanisms involving oxidative stress-mediated ferroptotic cell death and lipid peroxidation, influencing hypoxia-inducible factor-1α, insulin-like growth factor-1 (IGF-1), and leptin pathways. These pathways collectively regulate tumor proliferation, angiogenesis, and immune evasion; hence, their modulation may sensitize GBM to therapy. The study evaluated the therapeutic potential of artesunate in combination with anticancer drugs using in vitro GL261 glioblastoma cells and in vivo subcutaneous GL261 models. Clinically relevant agents representing distinct mechanisms, temozolomide, cyclophosphamide, paclitaxel, imatinib, and thymoquinone, were tested. Tumor volume, body weight, and serum biochemical parameters (IL-6, IGF-1, HIF-1α, and leptin) were analyzed, along with CD3 + T cell infiltration by immunohistochemistry. Combination treatments, particularly artesunate with temozolomide or paclitaxel, produced marked tumor regression compared with controls. Serum biomarker modulation and enhanced infiltration of CD3 + T cells indicated activation of ferroptotic and immune-mediated anti-tumor mechanisms, with minimal systemic toxicity. Artesunate potentiates the antitumor efficacy of standard chemotherapeutic agents through mechanisms involving ferroptosis and immune modulation, promoting a tumor-suppressive microenvironment. These findings support further mechanistic and translational studies toward developing ferroptosis-driven multimodal therapies for resistant glioblastomas.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the mechanism by which triphenyl phosphate promotes malignant phenotypes in bladder and kidney cancer through MMP9 based on bioinformatics analysis and experimental validation.","authors":"Hao Wang, Hongquan Liu, Qian Li, Fengze Sun, Jian Ma, Jitao Wu","doi":"10.1007/s10238-026-02159-7","DOIUrl":"https://doi.org/10.1007/s10238-026-02159-7","url":null,"abstract":"<p><p>Background Bladder and kidney cancer burden rises globally, with environmental toxicants driving their progression. Methods We integrated global epidemiological analysis, single-cell transcriptomics, cell-cell communication analysis, epithelial subclustering, pseudotime inference, toxicological target prediction, survival modeling, cross-cohort validation, single-cell virtual knockout, spatial transcriptomic deconvolution, molecular docking/dynamics, CETSA, and in vitro assays to define a shared molecular interface linking triphenyl phosphate (TPP) to bladder and kidney cancer. Results Both malignancies exhibited age- and SDI-associated burden patterns. Single-cell profiling identified conserved epithelial, stromal, and immune ecosystems, with tumor epithelial cells occupying central positions in intercellular communication networks. Epithelial subclustering revealed a reproducible EMT-high subcluster 4 in both cancers, which localized to a terminal-like pseudotime state and was associated with poor survival. Predicted TPP targets intersected with subcluster 4 signatures and converged on extracellular matrix organization, adhesion, and leukocyte transendothelial migration pathways. Integrative survival modeling and multi-cohort validation identified MMP9 as a robust prognostic candidate associated with tumor progression. Importantly, single-cell virtual knockout of MMP9 revealed convergent remodeling of proliferative, inflammatory, hypoxia-related, and stress-response programs across bladder and renal cancer epithelial cells, highlighting conserved regulatory circuitry. Spatial transcriptomics further localized MMP9 to macrophage- and fibroblast-enriched niches in both tumor types. Structural modeling and CETSA supported an interaction between TPP and MMP9. Experimentally, TPP upregulated MMP9 at both mRNA and protein levels in T24 and 786-O cells; higher concentrations reduced viability, whereas lower concentrations enhanced migration and clonogenic growth. Conclusions TPP promotes the malignant phenotypes of bladder and kidney cancer via MMP9, which is validated by virtual knockout and in vitro experiments.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal dynamic changes during the progression of myelodysplastic neoplasms to secondary acute myeloid leukemia: a paired-sample comparison.","authors":"Che-Wei Ou, Hsiao-Wen Kao, Tung-Liang Lin, Ming-Chung Kuo, Jin-Hou Wu, Hung Chang, Lee-Yung Shih","doi":"10.1007/s10238-026-02242-z","DOIUrl":"https://doi.org/10.1007/s10238-026-02242-z","url":null,"abstract":"<p><p>Patients with myelodysplastic neoplasms (MDS) have a risk of secondary acute myeloid leukemia (sAML) transformation, but previous studies on the paired samples at both MDS and sAML were very rare. This study aimed to investigate the genetic changes during the progression from MDS to sAML by comparing both phases of MDS at diagnosis and sAML in the same individuals. Seventy-nine paired matched samples of MDS at diagnosis and sAML phase were examined for 32 gene mutations commonly occurring in myeloid neoplasms, including epigenetic regulators, cohesin complex, spliceosome complex, signaling pathway, tumor suppressors, and transcription factors by next-generation sequencing. The acquisition of gene mutations involving signaling pathway and transcription factors was significantly more frequent during the progression to sAML compared to other groups of genes. Mutations involving epigenetic regulators, cohesin complex, and spliceosome complex were generally stable or expanded when disease progressed. Loss of gene mutations was rare, and all mutations showed no apparent decline in their variant allele frequencies except STAG2 mutation. RUNX1 mutations were characterized by acquisition or clonal expansion with no loss or decline during disease progression. TP53 mutations exhibit unique mutational complexity and evolutionary patterns. The dynamic distribution pattern of various gene mutations remained similar regardless of BM blast counts at MDS or the rate of disease progression. Our results demonstrated a distinct pattern of clonal changes in different groups of gene mutations during the progression from MDS to sAML.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silibinin promotes hepatocyte proliferation through PINK1/Parkin-mediated mitophagy to alleviate acetaminophen-induced liver injury.","authors":"Fengming Xu, Mohamed Albadry, Olaf Dirsch, Uta Dahmen","doi":"10.1007/s10238-026-02218-z","DOIUrl":"10.1007/s10238-026-02218-z","url":null,"abstract":"<p><p>Acetaminophen (APAP) intoxication is a common cause of liver injury. Silibinin has demonstrated potent hepatoprotective properties. However, its underlying mechanisms in APAP-induced liver injury (AILI) remain unclear. Autophagy is a critical adaptive response in AILI, contributing to the clearance of damaged mitochondria and the attenuation of oxidative stress. Therefore, we focused primarily on investigating the role of autophagy in mediating the hepatoprotective effects of silibinin. The effects of silibinin were evaluated in both AML12 cells and a C57BL/6J mouse model of AILI. Both the in vitro and in vivo experiments comprised four groups: a control group, an AILI model group, a silibinin treatment group, and a silibinin plus autophagy inhibitor group using PINK1-siRNA in cell culture and 3-Methyladenine in the animal experiment. Following induction of the AILI model in mice with APAP at a dose of 300 mg/kg, the animals received the designated interventions for five consecutive days. Histopathological alterations were assessed using hematoxylin-eosin staining. Hepatocyte proliferation and apoptosis were evaluated using the CCK-8 assay and immunohistochemical staining for Ki-67 and cleaved caspase-3, respectively, as well as ELISA for Cyclin D1. Liver function was assessed by serum biochemical analysis of alanine aminotransferase, aspartate aminotransferase, total bilirubin, and albumin. Mitochondrial oxidative stress-related parameters, including superoxide dismutase and malondialdehyde, were measured using colorimetric assays. The expression of autophagy-related genes and proteins (PINK1, Parkin, AMPK, LC3 and p62) was analyzed by quantitative PCR, immunofluorescence, and Western blotting. Transmission electron microscopy was employed to examine mitochondrial ultrastructure and the formation of autolysosomes in mouse liver tissue. In AML12 cells, silibinin mitigated AILI by activating the PINK1/Parkin pathway, thereby promoting mitophagy and enhancing cell proliferation. Co-treatment with autophagy inhibitor PINK1-siRNA attenuated these protective effects of silibinin. In AILI mice, silibinin treatment markedly improved liver function, attenuated inflammatory responses, restored mitochondrial function, and enhanced hepatocyte proliferation. These improvements were associated with increased LC3-II expression and reduced p62 accumulation, indicating enhanced autophagic activity. Notably, the protective benefits of silibinin were significantly attenuated by the autophagy inhibitor 3-Methyladenine. Our findings suggest that silibinin protects against AILI by activating PINK1/Parkin-dependent mitophagy, which mitigates oxidative stress and inflammation while promoting hepatocyte regeneration.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond polarization: a receptor-centered framework for macrophage function and therapy in skin diseases.","authors":"Yirou Zhu, Huiyi Yao, Wenzhong Xiang","doi":"10.1007/s10238-026-02194-4","DOIUrl":"https://doi.org/10.1007/s10238-026-02194-4","url":null,"abstract":"<p><p>Macrophages are key regulators of cutaneous immunity, but the traditional M1/M2 polarization model cannot fully explain their functional diversity across skin diseases. In this narrative review, we use selected skin diseases to discuss a receptor-centered view of macrophage function and to illustrate a modular \"receptor-pathway-effector\" framework. This perspective places macrophage receptors at the upstream sensing level, where microbial products, tissue damage signals, cytokines, immune complexes, stromal cues, and tumor-derived signals are translated into inflammatory, reparative, fibrotic, or immunosuppressive programs. We summarize representative receptor modules, including pattern-recognition receptors, cytokine and chemokine receptors, Fc and complement receptors, scavenger and efferocytosis receptors, and inhibitory checkpoint receptors. Across psoriasis, atopic dermatitis, autoimmune blistering diseases, lupus, systemic sclerosis, sarcoidosis, leprosy, melanoma, cutaneous T-cell lymphoma, diabetic wounds, and radiation-induced skin injury, these modules help explain macrophage involvement in inflammation, remodeling, host defense, impaired repair, and tumor immune escape. We also discuss selected biomarker and therapeutic examples, while distinguishing clinically explored approaches from preclinical or emerging concepts. This receptor-centered perspective may complement existing views of macrophage heterogeneity and provide a clearer way to link receptor signals with disease-related macrophage functions.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum GRP78 as a potential biomarker for early liver injury and active fibrogenesis in alcohol-associated liver disease.","authors":"Yongping Liu, Yaojie Shen, Yuxia Yu, Ying Meng, Yan Zheng, Xinyu Jiang, Wei Huang, Kai Yu, Yuan Chen, Xiaoying Wu, Cuirong Chen, Yan Liu","doi":"10.1007/s10238-026-02219-y","DOIUrl":"https://doi.org/10.1007/s10238-026-02219-y","url":null,"abstract":"<p><p>Alcohol-associated liver disease(ALD) is an important cause of liver-related lesions and death, mainly caused by long-term or excessive alcohol consumption.Reactive oxygen species (ROS) produced during alcohol metabolism induce an oxidative stress response, which GRP78 playing an important regulatory role. This study aims to investigate the relationship between serum GRP78 levels and liver fibrosis/cirrhosis in ALD patients. A case control study was conducted, involving ALD patients (n = 122) and healthy participants (n = 28). Liver steatosis and fibrosis/cirrhosis was assessed by transient elastography (TE) and biochemical parameters were collected. Serum GRP78 was measured by sandwich ELISA based on two monoclonal anti-GRP78 antibodies and calibrated with a standard of recombinant GRP78. Serum GRP78 levels increased in alcohol-associated steatohepatitis and alcoholic hepatitis patients correlated with early fibrosis severity (F1 fibrosis stage), but were significantly downregulated in patients with cirrhosis (F4 fibrosis stage). Furthermore, serum GRP78 levels showed a weak negative correlation with liver stiffness measurements (LSM; r = - 0.2064, p = 0.0365) and demonstrated a notable association with the severely advanced fibrotic stage in ALD patients, while showing no significant correlation with the controlled attenuation parameter (CAP) associated with liver steatosis. This study suggests that serum GRP78 is a potential noninvasive biomarker for early liver injury and active fibrogenesis in ALD patients. When combined with LSM, it improves diagnostic accuracy for advanced fibrosis and cirrhosis.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UBA2: the gatekeeper of the sumoylation pathway and its multifaceted roles in human diseases and therapeutic prospects.","authors":"Yi Liu, Qi Deng, Yang Qu, Minming Yi, Taiqiang Wang, Xuan Li, Rong Zhang, Yongkang Wu","doi":"10.1007/s10238-026-02239-8","DOIUrl":"https://doi.org/10.1007/s10238-026-02239-8","url":null,"abstract":"<p><p>Ubiquitin-like modifier-activating enzyme 2 (UBA2), the core catalytic subunit of the ubiquitin-activating enzyme (E1) for the small ubiquitin-like modifier (SUMO)ylation pathway, is the \"gatekeeper\" determining cellular SUMOylation levels. However, a systematic, cross-disease integration of its pathogenic mechanisms and translational value in human diseases is currently lacking. In this review, a disease taxonomy framework was used for the first time to systematically elucidate the multidimensional pathogenic mechanisms of UBA2 in tumors, developmental malformations, autoimmune diseases, and infectious diseases. Research indicates that functional dysregulation of UBA2 is a central node connecting diverse diseases: Driving malignant progression and therapy resistance in tumors, causing congenital malformations during development, acting as a pathogenic factor or autoantigen in autoimmunity, and being targeted by various pathogens for immune evasion. Based on its pivotal role, UBA2 has emerged as an important prognostic biomarker and therapeutic target, with related inhibitors demonstrating promise in preclinical studies. This article further elucidates the strategies and challenges in the clinical translation of precision therapies targeting UBA2, providing a theoretical foundation and translational roadmap.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}