Cell and Bioscience最新文献

{"title":"Comprehensive analysis of the critical role of the epithelial mesenchymal transition subtype - TAGLN-positive fibroblasts in colorectal cancer progression and immunosuppression.","authors":"Junli Zhang, Xinxin Jin, Yachao Hou, Biao Gu, Hongwei Li, Li Yi, Wenjuan Wu, Shangshang Hu","doi":"10.1186/s13578-025-01405-x","DOIUrl":"10.1186/s13578-025-01405-x","url":null,"abstract":"<p><p>Epithelial-mesenchymal transition (EMT) plays a pivotal role in tumor metastasis and immune suppression in colorectal cancer (CRC). However, the specific mechanisms of EMT and its relationship with the clinical prognosis and immunotherapy response in CRC patients remain unclear. In this study, we identified TAGLN-positive fibroblasts (TAGLN⁺Fib) as a cancer-associated fibroblast (CAF) subtype within the tumor microenvironment (TME) that promotes tumor metastasis and immune evasion. High EMT scores, strongly associated with TAGLN expression, were correlated with advanced tumor stages, poor prognosis, and resistance to immunotherapy. Functional experiments demonstrated that TAGLN knockdown significantly reduced CRC cell proliferation, migration, and EMT phenotypes in vitro and suppressed tumor growth in vivo. Furthermore, TAGLN⁺Fib closely interacted with MMP7-positive tumor epithelial cells and SPP1-positive macrophages, forming a pro-metastatic and immunosuppressive network. An EMT-TME risk model constructed using TAGLN⁺Fib exhibited robust predictive power for CRC prognosis and immunotherapy response. This study reveals the association of EMT scores with CRC prognosis and immunotherapy response, highlights TAGLN⁺Fib's critical role in tumor progression, and develops an EMT-TME risk model, offering insights for personalized CRC treatment and precision medicine.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"66"},"PeriodicalIF":6.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia-ischemia and sexual dimorphism: modeling mitochondrial dysfunction using brain organoids.","authors":"Romane Gaston-Breton, Clémence Disdier, Henrik Hagberg, Aloïse Mabondzo","doi":"10.1186/s13578-025-01402-0","DOIUrl":"10.1186/s13578-025-01402-0","url":null,"abstract":"<p><p>Hypoxic-ischemic encephalopathy (HIE) is a leading cause of neurodevelopmental morbidities in full-term infants. There is strong evidence of sexual differences in hypoxic-ischemic (HI) injury where male neonates are at higher risk as they are subject to more pronounced neurological deficits and death than females. The cellular and molecular mechanisms underlying these sexual discrepancies in HI injury are poorly understood. Mitochondrial dysregulation has been increasingly explored in brain diseases and represents a major target during HI events. In this review, we discuss (1) different mitochondrial functions in the central nervous system (2), mitochondrial dysregulation in the context of HI injury (3), sex-dependent mitochondrial pathways in HIE and (4) modeling of mitochondrial dysfunction using human brain organoids. Gaining insight into these novel aspects of mitochondrial function will offer valuable understanding of brain development and neurological disorders such as HI injury, paving the way for the discovery and creation of new treatment approaches.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"67"},"PeriodicalIF":6.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of ZBED3 in PALD1/PIP2- dependent calcium homeostasis during oocyte maturation.","authors":"Danyu Ni, Qijun Xie, Yuting Chen, Yi Wei, Peng Lang, Xiaodan Shi, Ye Yang, Xiufeng Ling, Chun Zhao","doi":"10.1186/s13578-025-01404-y","DOIUrl":"10.1186/s13578-025-01404-y","url":null,"abstract":"<p><p>Zinc Finger BED-Type Containing 3 (ZBED3) had been shown to be a novel component of the subcortical maternal complex (SCMC). In previous reports, ZBED3 depletion leads to asymmetric zygotic division and aberrant distribution of organelles in both oocytes and zygotes. However, the precise mechanism through which ZBED3 exerts its effects remains to be elucidated. To fill this gap, in this study, we generated Zbed3 gene knockout mice by using CRISPR/cas9 gene-editing technique to generate homozygous Zbed3^-/- female mice. A series of previously unreported phenotypes in oocytes were observed, including decreased fertility, abnormal spindle formation and migration, increased polyspermic fertilization, abnormal distribution of cortical granules (CGs), and disrupted calcium oscillations. To investigate the molecular mechanisms underlying the function of ZBED3 during oocyte maturation, we employed miniTurbo biotin ligase-based proximity labeling combined with mass spectrometry to identify protein interactomes in transfected HEK293 cells. OF the 187 ZBED3-interacting proteins, paladin 1 containing a phosphatase domain (PALD1) and E3 ubiquitin ligase makorin-1 (MKRN1) exhibited the highest fold changes and were subsequently validated. ZEBD3 suppressed PALD1 levels by enhancing its degradation via the ubiquitination-proteasome pathway. Depletion of Zbed3 results in an abnormal accumulation of PALD1. The ectopic overexpression of PALD1 recapitulates the phenotypic defects observed in Zbed3-deficient oocytes and early embryos. Moreover, knockdown of PALD1 partially rescued the oocyte maturation defects induced by Zbed3 depletion. Paladin is an endosomal phosphatidylinositol 4,5-bisphosphate (PIP2) phosphatase which directly modulates phosphoinositide metabolism by catalyzing the removal of phosphate groups from phosphoinositides. Furthermore, PALD1 overexpression reduced Ca²⁺ release from the endoplasmic reticulum (ER) by inhibiting its downstream target PIP2. Our study demonstrates that ZBED3 may regulate PIP2 protein levels by modulating the ubiquitin-proteasomal degradation of PALD1, thereby influencing oocyte maturation and providing a novel approach for assessing oocyte quality and developmental potential.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"68"},"PeriodicalIF":6.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological function of RNA-binding proteins in myocardial infarction: a potential emerging therapeutic limelight.","authors":"Chenyang Jin, Yutong Ye, Longzhe Gao, Zikan Zhong, Changzuan Zhou, Xiaoyu Wu, Xudong Li, Genqing Zhou, Songwen Chen, Yong Wei, Lidong Cai, Shaowen Liu, Juan Xu","doi":"10.1186/s13578-025-01408-8","DOIUrl":"10.1186/s13578-025-01408-8","url":null,"abstract":"<p><p>Myocardial infarction (MI) is currently one of the most fatal cardiovascular diseases worldwide. The screening, treatment, and prognosis of MI are top priorities for cardiovascular centers globally due to its characteristic occult onset, high lethality, and poor prognosis. MI is caused by coronary artery occlusion induced by coronary atherosclerotic plaque blockage or other factors, leading to ischemic necrosis and apoptosis of cardiomyocytes. Although significant advancements have been made in the study of cardiomyocytes at the cellular and molecular levels, RNA-binding proteins (RBPs) have not been extensively explored in the context of MI. RBPs, as key regulators coordinating cell differentiation and tissue homeostasis, exhibit specific functions in gene transcription, RNA modification and processing, and post-transcriptional gene expression. By binding to their target RNA, RBPs coordinate various RNA dynamics, including cellular metabolism, subcellular localization, and translation efficiency, thereby controlling the expression of encoded proteins. Classical RBPs, including HuR, hnRNPs, and RBM family molecules, have been identified as critical regulators in myocardial hypoxia, oxidative stress, pro-inflammatory responses, and fibrotic repair. These RBPs exert their effects by modulating key pathophysiological pathways in MI, thereby influencing specific cardiac outcomes. Additionally, specific RBPs, such as QKI and fused in sarcoma (FUS), are implicated in the apoptotic pathways activated during MI. This apoptotic pathway represents a significant molecular phenotype in MI, offering novel perspectives and insights for mitigating cardiomyocyte apoptosis and attenuating the progression of MI. Therefore, this review systematically summarizes the role of RBPs in the main pathophysiological stages of MI and explores their potential therapeutic prospects.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"65"},"PeriodicalIF":6.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intermittent fasting and metabolic dysfunction-associated steatotic liver disease: the potential role of the gut-liver axis.","authors":"Zhaoxi Zhang, Alice Pik-Shan Kong, Vincent Wai-Sun Wong, Hannah Xiaoyan Hui","doi":"10.1186/s13578-025-01406-w","DOIUrl":"10.1186/s13578-025-01406-w","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health concern linked to the increasing prevalence of metabolic syndrome, including obesity and type 2 diabetes (T2D). MASLD remains a significant clinical challenge due to the absence of effective therapeutic interventions. Intermittent fasting (IF) has emerged as a promising non-pharmacological strategy for managing MASLD. Although the exact mechanisms underpinning the possible beneficial effects of IF on MASLD are not yet fully elucidated, the gut microbiota and its metabolic byproducts are increasingly recognized as potential mediators of these effects. The gut-liver axis may act as an important conduit through which IF exerts its beneficial influence on hepatic function. This review comprehensively examines the impact of various IF protocols on gut microbiota composition, investigating the resultant alterations in microbial diversity and metabolomic profiles, and their potential implications for liver health and the improvement of MASLD.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"64"},"PeriodicalIF":6.1,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AgRP mediated calcium Inhibition of feeding via the vagal afferent nerve-brain pathway.","authors":"Aru Su, Linghui Pan, Qian Zhou, Qin Zhu, Ruihua Li, Mingming Liu, Ruifan Wu, Lina Wang, Songbo Wang, Qingyan Jiang, Gang Shu, Canjun Zhu","doi":"10.1186/s13578-025-01409-7","DOIUrl":"10.1186/s13578-025-01409-7","url":null,"abstract":"<p><p>Obesity poses serious health risks and is trending younger, developing effective strategies to prevent obesity is crucial. Calcium intake is a potential strategy to reduce weight/fat, as it generally enhances the body's energy metabolism. However, calcium's effects on appetite and its specific mechanisms remain unclear. To investigate these questions, we administered calcium orally to fasted mice and found that calcium inhibited food intake during the first 3 h. Long-term calcium supplementation in water decreased HFD intake, weight gain, and fat deposition while increasing energy metabolism in young mice. Mechanistically, calcium activated the vagal afferent nerves and inhibited ARC^AgRP neurons-key appetite regulation neuron. What's more, these effects are blunted by chemogenetic inhibition of gastrointestinal intestinal vagal afferent nerves or activation of ARC^AgRP neuronal activity. Overall, we showed that ingested calcium activates vagal afferent nerves, inhibiting the activity of ARC^AgRP neurons, thereby reducing food intake. This study supports calcium's role in obesity dietary therapy.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"63"},"PeriodicalIF":6.1,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tie2-expressing monocytes/macrophages promote angiogenesis in chronically ischaemic brain tissue.","authors":"Chuyang Tai, Cong Ling, Yang Yang, Baoyu Zhang, Jun Sun, Ni Mo, Tao Sun, Lixin Huang, Cian Yao, Hui Wang, Chuan Chen","doi":"10.1186/s13578-025-01401-1","DOIUrl":"10.1186/s13578-025-01401-1","url":null,"abstract":"<p><strong>Background: </strong>Over half of patients with chronically ischaemic cerebrovascular disease (CICD) exhibit poor revascularization potential. Tie2-expressing monocytes/macrophages (TEMs) have been reported to promote angiogenesis in tumour tissue; however, whether TEMs promote angiogenesis in chronically ischaemic brain tissue (CIBT) and the regulatory mechanism through which TEMs are recruited to CIBT remain unclear.</p><p><strong>Methods: </strong>We first analysed the proportion of TEMs in blood from the internal jugular veins (IJVs) of CICD patients and then isolated TEMs for coculture with human umbilical vein endothelial cells (HUVECs) and for intraventricular injection into nude mice to explore the proangiogenic effects of TEMs in CIBT. Then, molecular biology experiments were performed to verify the upstream regulatory mechanism of the ANGPT2-Tie2 axis, and cell transfection experiments were conducted to confirm the regulatory effects of the detected pathway on Tie2 receptors on the endothelial cell surface. Additionally, a 2-vessel occlusion plus encephalomyosynangiosis rat model was established to confirm the recruitment mechanism of TEMs in CIBT and their ability to improve cerebral blood perfusion (CBP) and cognitive function.</p><p><strong>Results: </strong>The proportion of TEMs from the IJV blood of CICD patients significantly increased, especially in patients who exhibited Matsushima Grade-A revascularization. The viability of HUVECs cocultured with TEMs was significantly increased, and CBP and the expression of CD31 in the CIBT of nude mice treated with TEMs were significantly increased. The above increases were positively correlated with the concentration of TEMs used for coculture and intraventricular injection. Moreover, molecular biology experiments indicated that miR-126-5p can directly bind to the 3'UTR of TRPS1 mRNA and that TRPS1 can directly bind to the promoter of Angpt2. HUVECs transfected with miR-126-5p mimics presented significantly decreased TRPS1 expression, a reduced pTie2/Tie2 ratio, increased ANGPT2 expression, and increased cell viability. Finally, significantly increased TEMs infiltration, downregulated TRPS1 expression, and upregulated ANGPT2, CD31, VEGFA, and IGF1 expression were detected in the CIBT of the rats transfected with the miR-126-5p agomir, accompanied by significant improvements in CBP and cognitive function.</p><p><strong>Conclusions: </strong>TEMs promote angiogenesis in CIBT through a paracrine mechanism, and the recruitment of TEMs to CIBT is regulated by the miR-126-5p/TRPS1/ANGPT2 pathway.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"62"},"PeriodicalIF":6.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The HNRNPC/CELF2 signaling pathway drives glycolytic reprogramming and mitochondrial dysfunction in drug-resistant acute myeloid leukemia.","authors":"Xiang Ma, Haodong Li, Ziqi Zhao, Changchun Li, Man Wang, Lele Zhang, Yutong Zhao, Haipeng Su, Feng Wang, Jiai Hua","doi":"10.1186/s13578-025-01386-x","DOIUrl":"10.1186/s13578-025-01386-x","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is an aggressive cancer with high treatment resistance, often leading to poor patient outcomes. Metabolic reprogramming plays a critical role in AML progression, influencing drug resistance (DR) and tumor survival. This study investigates the HNRNPC/CELF2 signaling pathway and its impact on AML cell metabolism and DR.</p><p><strong>Results: </strong>The study identified that HNRNPC regulates the expression of CELF2 through m6 A modification. In drug-resistant AML cells, increased HNRNPC expression and decreased CELF2 expression were associated with upregulated glycolysis, enhanced glucose consumption, lactate production, and mitochondrial dysfunction. Knockdown of HNRNPC reduced glycolysis and cell invasion, while CELF2 knockdown reversed these effects. Conversely, HNRNPC overexpression enhanced glycolysis and cell migration, which were counteracted by CELF2 overexpression.</p><p><strong>Conclusions: </strong>The HNRNPC/CELF2 axis plays a pivotal role in metabolic reprogramming, driving AML progression and chemotherapy resistance. Targeting this pathway may offer new therapeutic strategies to overcome resistance and improve treatment outcomes in AML patients.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"61"},"PeriodicalIF":6.1,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization and prognostic of CD8 + TIM3 + CD101 + T cells in glioblastoma multiforme.","authors":"Hong-Liang Wang, Sai Li, Chun-Chun Ma, Xiang-Hu Zheng, Hao-Yuan Wu, Chen-Xi Chang, Zhi-Hao Yang, Jia-Wei Wang, Fa-Ming Pan, Bing Zhao","doi":"10.1186/s13578-025-01390-1","DOIUrl":"10.1186/s13578-025-01390-1","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma multiforme (GBM) is a pervasive and aggressive malignant brain tumor. In the tumor immune microenvironment, CD8 + TIM3 + CD101 + T cells (CCT cells) play a pivotal role in tumor progression and immune evasion. This study aimed to characterize differentially expressed genes (DEGs) in CCT cells, establish a prognostic model for GBM, and explore clinical implications.</p><p><strong>Methods: </strong>Analysis of data from TCGA, CGGA, and GEO databases included whole-genome expression profiles, clinical data, single nucleotide mutations, and single-cell RNA sequencing. DEGs were identified, and cell trajectories were constructed using Seurat, Monocle 2, and CellChat packages. Functional enrichment analysis was conducted with clusterProfiler, and a prognostic model was developed. Immune infiltration and drug sensitivity analyses were performed to evaluate therapeutic implications.</p><p><strong>Results: </strong>Eight distinct cell types were distinguished, encompassing T cells, macrophages, neurons, mural cells, endothelial cells, oligodendrocytes, fibroblasts, and B cells. Comparative analysis revealed differences in these cell types between GBM samples with new adjuvant therapy and initial diagnosis controls. Pseudotime analysis indicated CD8 + TIM3 + CD101-T cells as precursors to CCT cells, unveiling unique gene expression patterns during this transition. The prognostic model, incorporating 22 gene features via LASSO regression, demonstrated strong predictive ability through Receiver Operating Characteristic (ROC) curves. Analysis of 28 immune cell types revealed differences between high-risk and low-risk groups, providing insights into GBM's immune evasion mechanisms. Drug sensitivity analysis proposed potential therapeutic strategies for high-risk patients.</p><p><strong>Conclusion: </strong>This study offers an in-depth understanding of CCT cells in GBM, introducing a novel prognostic model and suggesting promising therapeutic approaches.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"60"},"PeriodicalIF":6.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disrupting lipid homeostasis with CAV2 in OSCC triggers apoptosis, lipolysis, and mitochondrial dysfunction by transcriptional repression of PPARγ.","authors":"Yuting Bai, Mingjing Jiang, Xiaojie Chen, Gang Zhou","doi":"10.1186/s13578-025-01399-6","DOIUrl":"https://doi.org/10.1186/s13578-025-01399-6","url":null,"abstract":"<p><strong>Background: </strong>Abnormal lipid droplet (LD) dynamics in oral squamous cell carcinoma (OSCC) indicate lipid metabolism alterations that facilitate malignancy progression. However, the specific mechanisms by which disruptions in lipid homeostasis affect malignancy processes remain poorly understood. This study investigated the role of LD-associated protein Caveolin2 (CAV2) in OSCC lipid homeostasis and progression.</p><p><strong>Methods: </strong>The clinical relevance of CAV2 in OSCC was assessed through transcriptomics, single-cell sequencing, and functional validation in OSCC cells. CAV2 knockdown via shRNA was used to analyze its effects on growth, apoptosis, lipid homeostasis, and mitochondrial function. RNA sequencing, lipidomics, and molecular docking elucidated mechanisms of lipid metabolic disruption. Lipolysis was evaluated via glycerol release, lipidomics, and expression of related genes and proteins. Seahorse assays were used to evaluate mitochondrial dysfunction by analyzing mitochondrial respiration, while additional experiments assessed ROS levels, MMP, morphology, mass, and organelle interactions. In vivo, studies examined tumor progression in nude mice implanted with CAV2-knockdown OSCC cells. The regulatory role of PPARγ on CAV2 was explored through bioinformatics, correlation analysis, and dual-luciferase assays. Coimmunoprecipitation assessed CAV2 and NCOR1 binding with PPARγ, while the PPARγ inverse agonist T0070907 was used to enhance NCOR1-mediated repression of CAV2.</p><p><strong>Results: </strong>CAV2 was upregulated in OSCC and correlated with poor clinical outcomes. CAV2 knockdown increased apoptosis, reduced proliferation, and disrupted lipid homeostasis, elevating polyunsaturated fatty acids (PUFAs). Regulatory networks responsible for PUFA accumulation were mapped in CAV2-knockdown OSCC cells, from upstream regulators to downstream effects. Furthermore, lipolysis and mitochondrial dysfunction were also enhanced following CAV2 silencing. In vivo, CAV2 knockdown suppressed OSCC progression. Mechanistically, PPARγ regulated CAV2 transcription via NCOR1, but OSCC cells disrupted this repression. The PPARγ inverse agonist T0070907 restored NCOR1-mediated repression, synergistically enhancing the effects of CAV2 knockdown on apoptosis, lipolysis, and mitochondrial dysfunction.</p><p><strong>Conclusions: </strong>Alteration of CAV2 disrupted lipid homeostasis and inhibited OSCC progression by affecting key processes, including apoptosis, lipolysis, and mitochondrial dysfunction. The disruption was driven by the dysregulation of the PPARγ/NCOR1 axis, highlighting the potential of targeting CAV2 and its interaction with PPARγ as a therapeutic strategy for OSCC.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"59"},"PeriodicalIF":6.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}