Cell Biology and Toxicology最新文献

{"title":"U2AF65 mediated circPVT1 promotes NSCLC cell proliferation and inhibits ferroptosis through the miR-338-3p/GPX4 axis.","authors":"Lujuan He, Zezhi Zhou, Jufen Wang, Jiehan Jiang, Shenggang Liu","doi":"10.1007/s10565-025-10028-4","DOIUrl":"10.1007/s10565-025-10028-4","url":null,"abstract":"<p><strong>Background: </strong>Dysregulation of circRNA expression is associated with increased metastasis and an adverse prognosis in non-small cell lung cancer (NSCLC). Herein, this study assessed the role and regulatory mechanism of circPVT1 in NSCLC development.</p><p><strong>Methods: </strong>CircPVT1 expression was determined using qPCR. Functional assays, including cell proliferation, colony formation, and ferroptosis-related measurements (ROS, MDA, SOD, GSH and Fe²⁺ levels), were conducted following circPVT1 knockdown. The interactions between RNA and protein were determined through RIP, dual-luciferase reporter and fluorescence in situ hybridization. Actinomycin D assay was employed to test circPVT1 stability. Additionally, tumor progression in vivo was evaluated in xenograft models with U2AF65 knockdown.</p><p><strong>Results: </strong>CircPVT1 was significantly elevated in NSCLC samples, correlating with worse clinical outcomes. Its knockdown resulted in diminished cell proliferation and increased ferroptosis. Mechanically, circPVT1 sponges miR-338-3p, facilitating GPX4 expression, which enhanced cell proliferation. U2AF65 bound to and stabilized circPVT1, promoting cell proliferation. In animal models, U2AF65 knockdown suppressed tumor progression by regulating the circPVT1/miR-338-3p/GPX4 signaling pathway.</p><p><strong>Conclusions: </strong>U2AF65 stabilizes circPVT1 to promote NSCLC advancement through miR-338-3p suppression and GPX4 upregulation. Thus, circPVT1 and U2AF65 may be potential therapeutic targets in NSCLC.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"84"},"PeriodicalIF":5.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985776","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":"Activation of CaMKII⁺ neurons in the paramedian raphe nucleus promotes general anesthesia in male mice.","authors":"Xuehan Li, Zhixiong Ma, Xueliang Liu, Chen Chen, Ziqing Yu, Di Sang, Tongfei Wang, Eric Erquan Zhang, Guangyou Duan, Dapeng Ju, He Huang","doi":"10.1007/s10565-025-10037-3","DOIUrl":"10.1007/s10565-025-10037-3","url":null,"abstract":"<p><p>General anesthesia (GA) is an essential clinical and surgical adjunct, widely recognized as the result of coordinated networks among numerous brain regions. Anesthetic drugs with different characteristics are associated with distinct networks of brain regions involved in anesthesia. Ciprofol, a novel intravenous anesthetic derived from structural modifications of propofol, has shown promise in clinical applications. However, the specific neuronal circuits and brain regions mediating their actions may differ. Moreover, the core brain regions that mediate the common anesthetic effects of these drugs remain unclear. In this research, we identified a central ensemble of brainstem neurons within the paramedian raphe nucleus (PMnR) using c-Fos staining in mice subjected to GA induced by continuous intravenous infusion of ciprofol and propofol. This neuronal population, primarily composed of CaMKIIa and Gad1-expressing cells, demonstrated consistent activation in reaction to ciprofol. Optogenetic activation of PMnR^CaMKIIa neurons induced a GA state under ciprofol pre-administration, while sole activation of PMnR^CaMKIIa neurons induced a motionless state in mice. In addition, conditional inhibition of these neurons resulted in resistance to GA. In summary, we highlight the PMnR as a brain target for ciprofol and propofol. Furthermore, CaMKIIa⁺ neurons in the PMnR emerge as active promoters of the anesthesia process, shedding light on a previously unrecognized key player in the intricate neural network orchestrating GA.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"83"},"PeriodicalIF":5.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984850","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":"Rap2a promotes cardiac fibrosis and exacerbates myocardial infarction through the TNIK/Merlin/YAP axis.","authors":"Zhibin Lang, Xiaozhen Fan, Lin Qiu, Shuhui Hou, Junhui Zhou, Hongqi Lin","doi":"10.1007/s10565-025-10036-4","DOIUrl":"https://doi.org/10.1007/s10565-025-10036-4","url":null,"abstract":"<p><p>Myocardial fibrosis constitutes the primary pathological characteristic of myocardial infarction (MI). The activation and proliferation of myocardial fibroblasts serve as crucial factors in the process of the development of fibrosis in the myocardium. Our research delved into the role that Rap2a plays in cardiac function as well as myocardial fibrosis, while its effects on cardial fibroblasts (CFs) proliferation, migration, and phenotypic transformation were also explored. Examination of the GEO database showed a notable increase in the expression of Rap2a within myocardial tissue from mice with MI compared to normal mice. Rap2a deficiency relieves MI in mice and restrains the phenotypic transition, proliferation, and migration of CFs. The absence of Rap2a mitigates MI in mice. Besides, it curbs the growth of CFs, restricts their movement, and prevents them from undergoing phenotypic conversion. Rap2a can bind to TNIK in myocardial fibroblasts and enhance TNIK expression; Merlin/YAP signaling pathway was assessed as a downstream target of TNIK to further elucidate the regulatory mechanism through which Rap2a influences cardiomyocytes. In conclusion, this study provides evidence that Rap2a promotes myocardial fibrosis through mediating the myofibroblast transformation, proliferation, and migration of CFs via the TNIK/Merlin/YAP pathway, thereby exacerbating symptoms of myocardial infarction.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"80"},"PeriodicalIF":5.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980452","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":"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}