Cell Biology and Toxicology最新文献

{"title":"Panoramic lead-immune system interactome reveals diversified mechanisms of immunotoxicity upon chronic lead exposure.","authors":"Yifan Hong, Tianbao Ye, Hui Jiang, Aiting Wang, Boqian Wang, Yiyang Li, Haiyang Xie, Hongyu Meng, Chengxing Shen, Xianting Ding","doi":"10.1007/s10565-025-10034-6","DOIUrl":"https://doi.org/10.1007/s10565-025-10034-6","url":null,"abstract":"<p><p>Lead exposure is of high prevalence, and over a billion people are chronically exposed to alarming level of lead. Human immune system is highly vulnerable to lead, but the underlying mechanism remains unknown. Using single-cell mass cytometry and mass spectrometry-based proteomics, we performed a panoramic survey of lead targets at both cellular and molecular levels in murine immune system upon chronic lead exposure. We produced a single-cell landscape of lead, thiol metabolism and lead-induced toxicity across all immune cell types. We found that immune cells with extreme thiol metabolism are the most sensitive upon chronic lead exposure. It shows that CD4 + T cells and neutrophils are the most sensitive to lead, which is due respectively to a molecular mechanism rooted in their characteristic thiol metabolic capacity. Meanwhile, we found that lead accumulation by RBC further inflicted secondary toxicity to RBC phagocytes in spleen, e.g. macrophages and neutrophils. Unlike CD4 + T cells, which can be rescued by supplementation with thiol chelator, lead toxicity in these phagocytes cannot be effectively mitigated by thiol chelators. Overall, it forms a multiscale panoramic lead-immune system interactome upon chronic lead exposure, which provides valuable information for proactive prevention, therapy formulation and public health evaluation.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"81"},"PeriodicalIF":5.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960167","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":"ELF4 improves sepsis-induced myocardial injury by regulating STING signaling-mediated T cells differentiation.","authors":"Yawen Zheng, Xiongjun Peng, Yusha Zhang, Ruilin Liu, Junke Long","doi":"10.1007/s10565-025-10029-3","DOIUrl":"https://doi.org/10.1007/s10565-025-10029-3","url":null,"abstract":"<p><p>Septic cardiomyopathy (SCM) is a common complication caused by sepsis. T cells differentiation is involved in SCM progression. However, the role and underlying mechanisms of T cells-mediated immunity in SCM remain unclear. This study aimed to investigate the role of STING-mediated T cells differentiation in SCM. Cecal ligation and puncture (CLP) surgery was conducted in mice to establish SCM model. The mice were injected intraperitoneally with STING agonist ADU-S100 and C-176 after modeling. Wild type (WT) mice and CD4-STING^-/- mice were employed. Besides, overexpressing vectors of ELF4 (oe-ELF4), short hairpin RNA targeting ELF4 (sh-ELF4) were transfected into 293T cells. STING signaling was found to be activated in sepsis-induced myocardial immune injury in mice. The administration of ADU-S100 exacerbated myocardial injury and inflammation, while C-176 alleviated these effects. Additionally, STING activation influenced T cells differentiation, with an increase in Th1 and Th17 cells and a decrease in Treg cells. Conditional knockout of STING in CD4⁺ T cells reduced Th1 and Th17 populations and improved myocardial function and histology. Furthermore, ELF4 was found to inhibit STING activation, reducing T cells differentiation into pro-inflammatory subsets. Overexpression of ELF4 in CD4⁺ T cells ameliorated myocardial damage and improved cardiac function in CLP mice, suggesting that the ELF4-STING signaling axis plays a protective role in sepsis-induced myocardial injury by regulating T cells differentiation.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"82"},"PeriodicalIF":5.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978247","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":"Mitigating chemotherapy-induced granulosa cell damage: role of hUCMSC-EVs in regulating the lncRNA HCP5-miR-20a-5p-YAP1 network.","authors":"Ying Xie, Xiaoqin Chen, Tong Liang, Ling Chen, Dan Liu","doi":"10.1007/s10565-025-10033-7","DOIUrl":"https://doi.org/10.1007/s10565-025-10033-7","url":null,"abstract":"<p><p>The substantial apprehension facing young cancer patients revolves around the onset of chemotherapy-induced premature ovarian failure (POF), primarily linked to damage inflicted upon granulosa cells (GCs). The inquiry delves into the protective role of extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) in mitigating chemotherapy-induced ovarian failure. Specifically, we investigated the mechanism by which hUCMSC-EVs deliver the long non-coding RNA (lncRNA) HCP5 to regulate DNA damage repair in GCs via the miR-20a-5p/YAP1 axis. The detection of differentially expressed lncRNAs in GC injury resulting from cyclophosphamide (CP) was conducted through transcriptome sequencing. hUCMSC-EVs were isolated, characterized, and co-cultured with CP-injured GCs. Functional assays such as CCK-8, TUNEL, and ELISA were performed to evaluate GC viability, apoptosis, and ovarian endocrine function. Experimental validation of the interactions involving HCP5, miR-20a-5p, and YAP1 was achieved through performing luciferase reporter assays, RNA immunoprecipitation experiments, and Western blot (WB) analyses. HCP5 was significantly enriched in hUCMSC-EVs and effectively delivered into GCs. This resulted in improved GC viability, reduced apoptosis, and enhanced DNA repair. Mechanistically, HCP5 sponged miR-20a-5p, leading to the upregulation of YAP1, which in turn mitigated CP-induced GC damage. In vivo experiments further demonstrated that hUCMSC-EVs prevented CP-induced POF through modulation of the HCP5-miR-20a-5p-YAP1 axis. Our research underscores the therapeutic potential of hUCMSC-EVs in delivering HCP5 to promote DNA repair in GCs, thereby preventing chemotherapy-induced POF. This study provides a novel molecular framework for future therapeutic strategies aimed at protecting ovarian function during chemotherapy.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"79"},"PeriodicalIF":5.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967600","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":"Lactate-induced macrophage HMGB1 lactylation promotes neutrophil extracellular trap formation in sepsis-associated acute kidney injury.","authors":"Siwei Wei, Zijuan Dai, Lei Wu, Zhen Xiang, Xiaoxiao Yang, Liubing Jiang, Zhen Du","doi":"10.1007/s10565-025-10026-6","DOIUrl":"https://doi.org/10.1007/s10565-025-10026-6","url":null,"abstract":"<p><strong>Background: </strong>Neutrophils play a key role in sepsis-associated acute kidney injury (SAKI), a common and life-threatening complication of organ failure. High mobility group box 1 (HMGB1) modulates inflammatory responses and the formation of neutrophil extracellular traps (NETs). The present work aimed to explore whether HMGB1 lactylation promotes NET formation and exacerbates SAKI.</p><p><strong>Methods: </strong>Venous blood samples were collected from healthy volunteers and SAKI patients. A SAKI mouse model was established using the cecal ligation and puncture method. A coculture system of macrophage-derived exosomes and neutrophils was established. Macrophage-derived exosomes were isolated and identified. ELISAs, immunofluorescence staining, coimmunoprecipitation, and Western blotting were utilized to determine protein levels.</p><p><strong>Results: </strong>Elevated blood lactate levels were associated with increased HMGB1 levels in patients with SAKI. In mouse models, lactate increased HMGB1 expression, promoted NET formation, and exacerbated SAKI. Lactate stimulated M1 macrophages to secrete exosomes, leading to the accumulation and release of HMGB1 in the cytoplasm. Additionally, lactate promoted HMGB1 lactylation in macrophages, triggering the release of mitochondrial DNA from neutrophils and activating the cyclic GMP‒AMP synthase/stimulator of interferon genes pathway.</p><p><strong>Conclusion: </strong>This study revealed that lactate-induced HMGB1 lactylation in macrophages plays a role in promoting NET formation in SAKI through the cGAS/STING pathway. These findings suggest that HMGB1 could be a potential target for therapeutic intervention in SAKI.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"78"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990043","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":"Mechanism of lncRNA gadd7 regulating mitofusin 1 expression by recruiting LSD1 to down-regulate H3K9me3 level, and mediating mitophagy in alveolar type II epithelial cell apoptosis in hyperoxia-induced acute lung injury.","authors":"Guoyue Liu, Guiyang Jia, Yingcong Ren, Cunzhi Yin, Xuan Xiao, Hang Wu, Jun Liu, Miao Chen","doi":"10.1007/s10565-025-10021-x","DOIUrl":"https://doi.org/10.1007/s10565-025-10021-x","url":null,"abstract":"<p><strong>Objective: </strong>Hyperoxic exposure induces acute lung injury (ALI). We analyzed the mechanism of long non-coding RNA (lncRNA) growth-arrested DNA damage-inducible gene 7 (gadd7) regulating mitofusin 1 (MFN1) in Hyperoxia-induced ALI (HALI) type II alveolar epithelial cell (AEC II) apoptosis.</p><p><strong>Methods: </strong>The HALI rat model was generated using hyperoxic induction and treated with shRNA-gadd7 and rapamycin (Rapa), with ALI, apoptotic level, total protein concentration and total cell, neutrophil and macrophage counts assessed. The HALI cell model was developed on hyperoxia-induced RLE-6TN cells and processed with oe-MFN1, si-gadd7 and Rapa. Cell viability, apoptosis, TOM20/LC3BII co-localization, mitochondrial membrane potential (MMP), superoxide dismutase activity, malonaldehyde, reactive oxygen species (ROS), tumor necrosis factor-α, interleukin (IL)-10, IL-6, IL-1β, gadd7, MFN1, Cleaved caspase-3, Cleaved poly (ADP-ribose) polymerase, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X, LC3BI/II, lysine-specific demethylase 1 (LSD1), p62, and H3K9me3 protein levels were measured. gadd7-LSD1 interaction was predicted and verified by RPISeq database, RIP, and RNA pull-down assay.</p><p><strong>Results: </strong>In HALI rats, gadd7 was up-regulated in lung tissues, and gadd7 silencing alleviated oxidative stress, ALI and apoptosis. gadd7 knockdown inhibited oxidative stress and apoptosis though MFN1, and mediated mitophagy (evidenced by diminished LC3BII/LC3BI ratio, TOM20/LC3BII co-localization and ROS level, and elevated p62 level and MMP), which were reversed by mitophagy activation. By recruiting LSD1 to down-regulate H3K9me3 level and promote MFN1 expression, gadd7-mediated mitophagy affected ALI and apoptosis in HALI rats.</p><p><strong>Conclusion: </strong>LncRNA gadd7 regulated MFN1 expression by recruiting LSD1 to down-regulate H3K9me3 level and mediate mitophagy, thereby promoting AEC II apoptosis in HALI.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"77"},"PeriodicalIF":5.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978149","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":"Effects of the LINC00641/miR-323a-3p/EIF4G2 axis on behaviors and brain monoamine neurotransmitters in chronic unpredictable mild stress mice.","authors":"Ziqiao Lin, Dong Qi, Yongbo Zhang","doi":"10.1007/s10565-025-10015-9","DOIUrl":"https://doi.org/10.1007/s10565-025-10015-9","url":null,"abstract":"<p><strong>Objective: </strong>This paper aimed to probe the role of the LINC00641/miR-323a-3p/EIF4G2 axis in regulating behavioral and brain monoamine neurotransmitter levels in a mouse model of depression induced by chronic unpredictable mild stress (CUMS).</p><p><strong>Methods: </strong>A CUMS-induced depression model was established in mice. A series of behavioral tests, comprising the sucrose preference, tail suspension, as well as forced swimming tests, were conducted. Levels of LINC00641, miR-323a-3p, and EIF4G2 in hippocampal tissues were measured. Biochemical indices, including 5-HT, NE, and DA, were analyzed. Hippocampal neuron structure and apoptosis were evaluated. The targeting relationship among LINC00641, miR-323a-3p, and EIF4G2 was validated experimentally.</p><p><strong>Results: </strong>CUMS mice exhibited reduced sucrose preference, prolonged immobilization time in behavioral tests, decreased 5-HT, NE, and DA levels, and increased hippocampal neuron apoptosis. Overexpression of LINC00641 or knockdown of miR-323a-3p significantly alleviated depression-like behaviors and restored monoamine neurotransmitter levels. LINC00641 regulated EIF4G2 expression by targeting miR-323a-3p, while miR-323a-3p and EIF4G2 also modulated depression through LINC00641.</p><p><strong>Conclusion: </strong>Upregulation of LINC00641 improves depression-like behaviors and enhances monoamine neurotransmission in CUMS mice via the miR-323a-3p/EIF4G2 axis, underscoring its potent as a therapeutic target for depression.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"76"},"PeriodicalIF":5.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984854","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":"SDH defective cancers: molecular mechanisms and treatment strategies.","authors":"Jiaer Wang, Tao Yuan, Bo Yang, Qiaojun He, Hong Zhu","doi":"10.1007/s10565-025-10022-w","DOIUrl":"https://doi.org/10.1007/s10565-025-10022-w","url":null,"abstract":"<p><p>Succinate dehydrogenase (SDH), considered as the linkage between tricarboxylic acid cycle (TCA cycle) and electron transport chain, plays a vital role in adenosine triphosphate (ATP) production and cell physiology. SDH deficiency is a notable characteristic in many cancers. Recent studies have pinpointed the dysregulation of SDH can directly result its decreased catalytic activity and the accumulation of oncometabolite succinate, promoting tumor progression in different perspectives. This article expounds the various types of SDH deficiency in tumors and the corresponding pathological features. In addition, we discuss the mechanisms through which defective SDH fosters carcinogenesis, pioneering a categorization of these mechanisms as being either succinate-dependent or independent. Since SDH-deficient and cumulative succinate are regarded as the typical features of some cancers, like gastrointestinal stromal tumors, pheochromocytomas and paragangliomas, we summarize the presented medical management of SDH-deficient tumor patients in clinical and preclinical, identifying the potential strategies for future cancer therapeutics.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"74"},"PeriodicalIF":5.3,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966971","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":"Lipotoxicity, lipid peroxidation and ferroptosis: a dilemma in cancer therapy.","authors":"Chuhan Ma, Huixin Hu, Hao Liu, Chongli Zhong, Baokang Wu, Chao Lv, Yu Tian","doi":"10.1007/s10565-025-10025-7","DOIUrl":"https://doi.org/10.1007/s10565-025-10025-7","url":null,"abstract":"<p><p>The vulnerability of tumor cells to lipid peroxidation, driven by redox imbalance and lipid overabundance within the tumor microenvironment (TME), has become a focal point for novel antitumor strategies. Ferroptosis, a form of regulated cell death predicated on lipid peroxidation, is emerging as a promising approach. Beyond their role in directly eliminating tumor cells, lipid peroxidation and its products, such as 4-hydroxynonenal (HNE), exert an additional influence by damaging DNA and shaping an environment conducive to tumor growth and metastasis. This process polarizes macrophages towards a pro-inflammatory phenotype, dampens the antigen-presenting capacity of dendritic cells (DCs), and undermines the cytotoxic functions of T and NK cells. Furthermore, it transforms neutrophils into pro-tumorigenic polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). The lipid peroxidation of stroma cells also contributes to tumor progression. Although advanced nanotherapies have shown the ability to target tumor cells precisely, they often overlook the nuanced effects of lipid peroxidation products. In this review, we highlight a synergistic mechanism in which lipid peroxidation products and ferroptosis contribute to an immunosuppressive state that is temporally distinct from cell death. This insight broadens our understanding of ferroptosis-derived immunosuppression, encompassing all types of immune cells within the TME. This review aims to catalyze further research in this underexplored area, emphasizing the potential of lipid peroxidation products to hinder the clinical translation of ferroptosis-based therapies.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"75"},"PeriodicalIF":5.3,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972981","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":"Ubiquitin-specific peptidase 10 attenuates bleomycin-induced pulmonary fibrosis via modulating autophagy depending on sirtuin 6-mediated AKT/mTOR.","authors":"Shitao Mao, Na Yu, Wei Wang, Yikai Mao, Ying Du, Qihe Zhao, Xiu Gu, Jian Kang","doi":"10.1007/s10565-025-10031-9","DOIUrl":"10.1007/s10565-025-10031-9","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF), characterized by fibroblast activation and collagen deposition, is a progressive lung disease that lacks effective interventions. Ubiquitin-specific peptidase 10 (USP10) acts as a multifunctional player in inflammatory response and progression of cancers, the effect on pulmonary fibrosis is unknown. Here, we demonstrated downregulated expression of USP10 in fibrotic lung tissues of IPF patients. In the current study, lung tissues were collected at the end of weeks 1, 2, or 3 post bleomycin (BLM)-intratracheal delivery. Consistently, USP10 expression levels were reduced after BLM challenge in a time-dependent manner. Mice treated with lentivirus overexpressing USP10 exhibited mitigative lung injury and reduced collagen deposition. USP10 overexpression enhanced autophagy in BLM-treated mouse lungs. Interestingly, the protective effect of USP10 was attenuated as the pulmonary autophagy flux was blocked by autophagy inhibitor 3-methyladenine (3-MA). Primary human and mouse lung fibroblasts were treated with pro-fibrotic TGF-β1 to verify the role of USP10 in vitro. Mechanically, the deubiquitinating enzyme USP10 interacted with Sirtuin 6 (Sirt6) and inhibited its degradation. Furthermore, USP10 overexpression inhibited the activation of Sirt6-mediated AKT/mTOR pathway in both lung tissues and fibroblasts. Our findings suggest that USP10 might attenuate pulmonary fibrosis through the promotion of Sirt6/AKT/mTOR-mediated autophagy. These data prioritize USP10 as a therapeutic target for treating IPF.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"73"},"PeriodicalIF":5.3,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12031808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954090","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":"Machine learning-based identification of cuproptosis-related lncRNA biomarkers in diffuse large B-cell lymphoma.","authors":"Wenhao Ouyang, Zijia Lai, Hong Huang, Li Ling","doi":"10.1007/s10565-025-10030-w","DOIUrl":"https://doi.org/10.1007/s10565-025-10030-w","url":null,"abstract":"<p><p>Multiple machine learning techniques were employed to identify key long non-coding RNA (lncRNA) biomarkers associated with cuproptosis in Diffuse Large B-Cell Lymphoma (DLBCL). Data from the TCGA and GEO databases facilitated the identification of 126 significant cuproptosis-related lncRNAs. Various feature selection methods, such as Univariate Filtering, Lasso, Boruta, and Random Forest, were integrated with a Transformer-based model to develop a robust prognostic tool. This model, validated through fivefold cross-validation, demonstrated high accuracy and robustness in predicting risk scores. MALAT1 was pinpointed using permutation feature importance from machine learning methods and was further validated in DLBCL cell lines, confirming its substantial role in cell proliferation. Knockdown experiments on MALAT1 led to reduced cell proliferation, underscoring its potential as a therapeutic target. This integrated approach not only enhances the precision of biomarker identification but also provides a robust prognostic model for DLBCL, demonstrating the utility of these lncRNAs in personalized treatment strategies. This study highlights the critical role of combining diverse machine learning methods to advance DLBCL research and develop targeted cancer therapies.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"72"},"PeriodicalIF":5.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985933","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}