Cell Biology and Toxicology最新文献

{"title":"Advances of NAT10 in diseases: insights from dual properties as protein and RNA acetyltransferase.","authors":"Bin Xiao, Shunhong Wu, Yan Tian, Weikai Huang, Guangzhan Chen, Dongxin Luo, Yishen Cai, Ming Chen, Yuqian Zhang, Chuyan Liu, Junxiu Zhao, Linhai Li","doi":"10.1007/s10565-024-09962-6","DOIUrl":"10.1007/s10565-024-09962-6","url":null,"abstract":"<p><p>N-acetyltransferase 10 (NAT10) is a member of the Gcn5-related N-acetyltransferase (GNAT) family and it plays a crucial role in various cellular processes, such as regulation of cell mitosis, post-DNA damage response, autophagy and apoptosis regulation, ribosome biogenesis, RNA modification, and other related pathways through its intrinsic protein acetyltransferase and RNA acetyltransferase activities. Moreover, NAT10 is closely associated with the pathogenesis of tumors, Hutchinson-Gilford progeria syndrome (HGPS), systemic lupus erythematosus, pulmonary fibrosis, depression and host-pathogen interactions. In recent years, mRNA acetylation has emerged as a prominent focus of research due to its pivotal role in regulating RNA stability and translation. NAT10 stands out as the sole identified modification enzyme responsible for RNA acetylation. There remains some ambiguity regarding the similarities and differences in NAT10's actions on protein and RNA substrates. While NAT10 involves acetylation modification in both cases, which is a crucial molecular mechanism in epigenetic regulation, there are significant disparities in the catalytic mechanisms, regulatory pathways, and biological processes involved. Therefore, this review aims to offer a comprehensive overview of NAT10 as a protein and RNA acetyltransferase, covering its basic catalytic features, biological functions, and roles in related diseases.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"17"},"PeriodicalIF":5.3,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892381","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":"AP-1 activates KCNN4-mediated Ca2⁺ signaling to induce the Th1/Th17 differentiation of CD4⁺ cells in chronic non-bacterial prostatitis.","authors":"Jingfei Teng, Zhuomin Jia, Feng Gao, Yawei Guan, Li Yao, Chong Ma, Zhihui Li, Xing Ai","doi":"10.1007/s10565-024-09967-1","DOIUrl":"10.1007/s10565-024-09967-1","url":null,"abstract":"<p><p>The intraprostatic inflammatory infiltrate is characterized by Th1 CD4⁺ T cells, and its molecular mechanism is not well defined. This study explored the mechanisms responsible for the alteration of Th1/Th17 differentiation of CD4⁺ T cells in chronic non-bacterial prostatitis (CNP). CNP rats were induced by the administration of testosterone and 17β-estradiol. The Th1/Th17 cell percentage was increased in the prostate tissue of CNP rats, which was accompanied by increased IL-2, IFN-γ, IL-17A, and IL-22 levels. Transcriptome sequencing was performed, followed by KEGG pathway enrichment analysis. Activator protein-1 (AP-1) was enhanced in CD4⁺ T cells from CNP rats, and its inhibitor SR11302 suppressed Th1/Th17 differentiation and delayed CNP. AP-1 transcriptionally activated the expression of KCNN4, which potentiated mTORC1 in CD4⁺ T cells by enhancing Ca2⁺ signaling, thereby promoting Th1/Th17 differentiation. Rapamycin-mediated autophagy activation reversed AP-1/KCNN4/mTORC1-promoted Th1/Th17 differentiation, thereby inhibiting CNP. These results suggest that AP-1-mediated KCNN4 transcription promotes the inhibition of autophagy by mTORC1 through Ca2⁺ signaling, which supports Th1/Th17 differentiation of CD4⁺ T cells, resulting in the transformation of CNP to prostatic intraepithelial neoplasia and adenocarcinoma.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"18"},"PeriodicalIF":5.3,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11680619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892397","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":"RBM19 promotes the progression of prostate cancer under docetaxel treatment via SNHG21/PIM1 axis.","authors":"Wei Zhuang, Siwei Xu, Qingliu He, Qingfu Su, Heyi Chen, Jiabi Chen, Congming Huang, Zhijiao You","doi":"10.1007/s10565-024-09985-z","DOIUrl":"10.1007/s10565-024-09985-z","url":null,"abstract":"<p><p>RBM family proteins plays the critical role in the progression of numerous tumors. However, whether RBM family proteins involved in prostate cancer (PCa) progression is remain elucidated. In our study, an RNAi screen containing shRNA library targeting 54 members of the RBM family was applied to identify the critical RBM proteins involved in prostate cancer progression under docetaxel treatment, and RBM19 was selected. RBM19 was up-regulated in PCa specimens and correlated with the prognosis and Gleason score of PCa patients. Functionally assays revealed that RBM19 promoted PCa progression under docetaxel treatment both in vivo and in vitro. Mechanistically, RBM19 could bind to LncRNA SNHG21, thereby increased SNHG21 expression through enhancing its stability. Furthermore, SNHG21 bind to PIM1 proteins and prevented it from ubiquitin-protease dependent degradation and ultimately enhancing mitochondrial homeostasis. Overall, our study indicates the RBM19/SNHG21/PIM1 axis may be the encouraging target for docetaxel-tolerance PCa treatment.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"19"},"PeriodicalIF":5.3,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11680647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892400","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":"Targeting CDK1 and copper homeostasis in breast cancer via a nanopolymer drug delivery system.","authors":"Nan Shang, Lisi Zhu, Yan Li, Chengyang Song, Xiaodan Liu","doi":"10.1007/s10565-024-09958-2","DOIUrl":"10.1007/s10565-024-09958-2","url":null,"abstract":"<p><p>The prevalence of breast cancer (BRCA) is notable in the female population, being a commonly diagnosed malignancy, where the management of copper levels is crucial for treatment success. This research aims to explore the influence of copper homeostasis on BRCA therapy, with a specific focus on the role of Cyclin-Dependent Kinase 1 (CDK1) and its relationship to copper regulation. A novel thermosensitive hydrogel incorporating nanoparticles (NPs) was engineered to synergize with the chemotherapy drug vincristine (VCR) in inhibiting tumor growth and metastasis. Through a comprehensive approach involving bioinformatics analyses, in vitro experiments, and in vivo models, the study identified CDK1 as a significant factor in BRCA progression under copper homeostasis. MBVP-Gel, a novel thermosensitive hydrogel incorporating NPs, was developed to enhance the delivery of chemotherapy drugs and regulate copper homeostasis in breast cancer treatment. The MBVP-Gel, formulated with copper chelation and VCR NPs, effectively suppressed CDK1 expression, thereby restraining BRCA cell growth and metastasis while enhancing the therapeutic impact of VCR. This investigation offers fresh insights and experimental validation on the interaction between copper homeostasis and BRCA, providing a valuable foundation for refining future treatment strategies. These findings underscore the potential advantages of targeting copper homeostasis and CDK1 in enhancing BRCA therapy, setting the stage for individualized interventions and improved patient consequences.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"16"},"PeriodicalIF":5.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892401","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":"HMGA1 influence on iron-induced cell death in Tfh cells of SLE patients.","authors":"Shan Zhao, Xiaotong Chen, Bohan Chang, Bailing Tian","doi":"10.1007/s10565-024-09955-5","DOIUrl":"10.1007/s10565-024-09955-5","url":null,"abstract":"<p><p>The autoimmune disorder known as Systemic Lupus Erythematosus (SLE) exhibits intricate features with abnormal immune responses leading to tissue injury. The generation of antibodies and the disruption of immune regulation heavily depend on the pivotal function of T follicular helper (Tfh) cells. Iron dysregulation is significant in autoimmune diseases, impacting immune cell function and disease progression. Our study investigates the role of the HMGA1/EZH2/STAT3/GPX4 axis in modulating Tfh cells and iron homeostasis in SLE. Abnormal Tfh cell populations in SLE patients demonstrate reduced susceptibility to iron-induced cell death, with HMGA1 identified as a key player in Tfh cell proliferation and sensitivity to iron-induced death. Experimental interventions reveal the inhibitory role of the HMGA1 axis in Tfh cells' susceptibility to iron-induced death, suggesting therapeutic avenues for SLE and related autoimmune disorders. Our study underscores the importance of iron homeostasis in autoimmune conditions, providing novel insights and treatment strategies for further research in this field.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"6"},"PeriodicalIF":5.3,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871559","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":"Investigating the role of Wnt3a and Wnt5a as critical factors of hepatic stellate cell activation in acute toxicant-induced liver injury.","authors":"Lauren N Rutt, David J Orlicky, Rebecca L McCullough","doi":"10.1007/s10565-024-09956-4","DOIUrl":"10.1007/s10565-024-09956-4","url":null,"abstract":"<p><p>Toxicant exposure can lead to acute liver injury, characterized by hepatic reprogramming and wound healing. Hepatic stellate cells (HSC) play a key role in liver regeneration during wound healing by secreting fibrogenic factors and production of extracellular matrix (ECM). However, repetitive injury to the liver can lead to extensive scarring and liver fibrosis, indicating HSCs coordinate both regeneration and disease. Because the factors contributing to HSC reprogramming during wound healing are not fully defined, we sought to further characterize morphogenic pathways of regeneration in an acute model of toxicant-induced liver injury¹. Wnt/β-catenin signaling has been recently associated with progressive liver fibrosis, but its role in HSC reprogramming is not well defined. Here, we investigated the canonical role of Wnt3a/Wnt5a on β-catenin-dependent HSC transdifferentiation and find that hepatic ECM gene expression is increased and associated with Wnt3a, Wnt5a, and their transducers (Frizzled-2 and Frizzled-7) after an acute exposure of the hepatotoxin, carbon tetrachloride(CCl₄₎. Moreover, we find exogenous Wnt3a and Wnt5a can accelerate spontaneous, culture-induced HSC activation in vitro as evidenced by increased total expression of fibrogenic factors, including Col1a1 and α-SMA. Challenge with Wnt3a induced canonical β-catenin-dependent transcription of axin2, which was attenuated by the Wnt coreceptor antagonist, Dickkopf-1 (DKK-1). These data support a role for canonical Wnt signaling as an additional mechanism by which HSCs dynamically respond to liver injury during the early wound healing response. New & noteworthy. This study elucidates novel mechanisms of fibrotic gene reprogramming in the liver. Specifically, we describe that Wnts and their transducers are increased during early liver injury which are associated with early fibrogenic responses and for the first time, causally link Wnts as direct inducers of HSC activation in the liver.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"5"},"PeriodicalIF":5.3,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871193","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":"Mechanistic insights into sevoflurane-induced hippocampal neuronal damage and cognitive dysfunction through the NEAT1/Nrf2 signaling axis in aged rats.","authors":"Yiliang Wang, Nu Li, Xiaoyu Chen, Yue Zhao, Letian Qu, Dasheng Cai","doi":"10.1007/s10565-024-09964-4","DOIUrl":"10.1007/s10565-024-09964-4","url":null,"abstract":"<p><p>The use of anesthetics during surgery can cause severe neurological damage and cognitive dysfunction in elderly patients. However, this health issue currently lacks corresponding therapeutic strategies. This research involved the utilization of single-cell RNA sequencing (scRNA-seq) and transcriptomic assessment to pinpoint crucial cell classifications and molecular pathways, as well as the lncRNA expression profiles, that undergo substantial alterations in aged rats experiencing sevoflurane-induced cognitive impairment. The results of our investigation pointed towards the enrichment of differentially expressed genes in neurons within the Nrf2/ARE signaling pathway, alongside an elevated expression of lncRNA NEAT1. Subsequently, by constructing a rat model to induce neuronal dysfunction with sevoflurane and performing experiments both in vivo and in vitro (including TUNEL staining, H&E staining, immunohistochemistry, immunofluorescence, and flow cytometry to assess apoptosis levels), we confirmed that NEAT1 inhibits the Nrf2/ARE/HO-1 pathway-related factors. Sevoflurane promotes oxidative stress and apoptosis in primary hippocampal neurons through the NEAT1/Nrf2/ARE/HO-1 axis. This study elucidates the molecular mechanism by which sevoflurane induces hippocampal neuronal damage and cognitive decline in elderly rats via the regulation of the lncRNA NEAT1/Nrf2 signaling axis. We discovered that upregulation of NEAT1 suppresses the Nrf2 signaling pathway, further inducing neuronal damage and cognitive dysfunction, furnishing an essential citation to grasp the molecular pathways involved in neuronal harm and devising corresponding treatment methodologies.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"13"},"PeriodicalIF":5.3,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871486","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":"M6A modification-mediated LIMA1 promotes the progression of hepatocellular carcinoma through the wnt-βcatenin/Hippo pathway.","authors":"Chao Zhang, Xiaoxiao Wang, Huangqin Song, Junlong Yuan, Xiaomin Zhang, Yiran Yuan, Zhuangqiang Wang, Zhang Lei, Jiefeng He","doi":"10.1007/s10565-024-09959-1","DOIUrl":"10.1007/s10565-024-09959-1","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC), considered as one of the most common and lethal cancers worldwide, has drawn significant attention from researchers.Extensively studied diverse cancers, the function of LIMA1 in tumorigenesis and cancer progression remains ambiguous.. Moreover, the role of LIMA1 in HCC remains controversial.</p><p><strong>Methods: </strong>The expression difference of LIMA1 in hepatocellular carcinoma, which was verified by TMT quantitative proteomics, immunohistochemistry, western blot, and the TCGA database, has been investigated in this study. Demonstrated by using transwell, cck8, sphere formation, and other experiments, the effects of LIMA1 on the migration, proliferation, stemness, and other aspects of hepatocellular carcinoma were significant. Moreover, the effect of LIMA1 on the wnt-βcatenin/Hippo pathway was revealed by using RNA sequencing and western blot, and the relationship between LIMA1 and βcatenin was verified by using COIP. Finally, the effect of m6a modification on LIMA1 was further verified using Western blotting, actinomycin D and MeRip experiments.</p><p><strong>Results: </strong>In HCC tissues and several HCC cell lines, LIMA1 was expressed at a relatively high level.LIMA1 positively regulated the invasion, migration, proliferation and stemness of hepatocellular carcinoma, and silencing of LIMA1 inhibited the tumorigenic ability of HCC cells in nude mice. Moreover, it was shown that LIMA1 can have an impact on the wnt-β-catenin/Hippo pathway. And silencing β-catenin suppressed the invasion, migration, proliferation and stemness of hepatocellular carcinoma cells mediated by LIMA1. Finally, it was further verified that the activation of LIMA1 in hepatocellular carcinoma cells is due to m6-methyladenosine methylation that is dependent on METTL3.</p><p><strong>Conclusions: </strong>In HCC, LIMA1 functions as a tumor promoter and engages with the WNT-β-catenin and Hippo signaling pathways,, affecting the characteristics of tumor cells. LIMA1 expression is regulated by METTL3-mediated m6A modification, leading to its high expression in HCC. Our research presents a hopeful objective for the detection and therapy of HCC.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"9"},"PeriodicalIF":5.3,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of gastric cancer stem cells with CD44 and Lgr5 double labelling and their initial roles on gastric cancer malignancy and chemotherapy resistance.","authors":"Zhida Chen, Yunhe Gao, Pengfei Zhang, Yi Liu, Bo Wei, Lin Chen, Hongqing Xi","doi":"10.1007/s10565-024-09960-8","DOIUrl":"10.1007/s10565-024-09960-8","url":null,"abstract":"<p><p>Accumulating evidences have indicated that cancer stem cells (CSCs) can initiate tumor progression and cause recurrence after therapy. However, specific markers of gastric CSCs (GCSCs) from different origins have not been comprehensively revealed. Here, we further detected whether cell populations labelled with CD44 and Lgr5, well-recognized stem markers for gastric cancer (GC), can better emphasize cancer initiation, therapeutic resistance and recurrence. Flow cytometry was utilized to sort the CD44 + Lgr5 + and CD44 + Lgr5- cells from GC cell line HGC-27 and primary GC cells. The influences of CD44 and Lgr5 GCSCs on the malignant behaviors and their potential mechanisms was investigated, respectively. In our study, we reported the identification and validation of CD44 + Lgr5 + cells that presented stronger stemness characteristics, as evidenced by increase of sphere forming ability, elevation of stem cell transcriptional activity. Additionally, CD44 + Lgr5 + double positive cells have lower apoptosis, greater chemotherapy resistance, and higher EMT capacity and LC3 density compared with CD44 + Lgr5- cells. Tumor xenograft experiments also verified the faster carcinogenesis of CD44 + Lgr5 + GCSCs. Furthermore, a series of key proteins in the Wnt, Hedgehog, Notch, and TGF-β pathways were elevated in the CD44 + Lgr5 + double positive subpopulation, except for Notch 1 and Smad 1. In conclusion, the binding of CD44 and Lgr5 can serve as a precise GCSCs marker that initiate malignant progression and chemotherapy resistance in GC by activating Wnt, Hedgehog, Notch, TGF-β pathways. Those evidences raise the needs to target both markers simultaneously as a potential approach for the GC treatment.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"12"},"PeriodicalIF":5.3,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870830","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":"E2F1-driven CENPM expression promotes glycolytic reprogramming and tumorigenicity in glioblastoma.","authors":"Zhiqiang Yi, Yanfei Jia, Runchun Lu, Chunwei Li, Long Wen, Xiangdong Yin, Junfei Yi, Liang Li","doi":"10.1007/s10565-024-09945-7","DOIUrl":"10.1007/s10565-024-09945-7","url":null,"abstract":"<p><p>Centromere protein M (CENPM), traditionally associated with chromosome segregation, is now recognized for its significant role in cancer biology. Particularly in glioblastoma (GBM), where less is known about CENPM compared to other centromere proteins (CENPs), it appears crucially involved in regulating tumor cell proliferation, invasion, and metabolic reprogramming-key factors in GBM's aggressiveness. Initial analyses using the GEPIA database (TCGA/GTEx datasets) reveal distinct patterns of CENPM expression in GBM, suggesting its potential as a therapeutic target. Our study manipulated CENPM expression through shRNA-mediated knockdown and vector-based overexpression in GBM cell lines LN229 and U251. Knockdown resulted in a 50% reduction in cell proliferation and a 70% decrease in invasion, accompanied by diminished glycolytic markers such as glucose consumption, lactate production, and ATP levels. Conversely, overexpression of CENPM enhanced both metabolic activity and invasive capacities. The introduction of the glycolytic inhibitor 2-DG effectively reversed the effects of CENPM modulation, highlighting a dependency on glycolytic pathways. Moreover, we identified E2F1 as a key regulator of CENPM, linking it to GBM's metabolic alterations. In vivo studies using a BALB/c nude mouse xenograft model demonstrated that CENPM knockdown significantly inhibits tumor growth, with treated groups showing a 60% reduction in tumor volume over four weeks. These findings underscore the E2F1-CENPM axis as a promising target for therapeutic strategies, aiming to disrupt the metabolic and invasive pathways facilitated by CENPM in GBM. These insights establish a foundation for targeting the metabolic dependencies of tumor cells, potentially leading to innovative treatments for GBM.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"4"},"PeriodicalIF":5.3,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871556","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}