Cellular & Molecular Biology Letters最新文献

{"title":"Immune cell aberrations in Systemic Lupus Erythematosus: navigating the targeted therapies toward precision management.","authors":"YuXian Wu, Wangzheqi Zhang, Yan Liao, Ting Sun, Yang Liu, Yaoyang Liu","doi":"10.1186/s11658-025-00749-z","DOIUrl":"10.1186/s11658-025-00749-z","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by multilayered dysregulation of immune cell homeostasis, spanning B cell effector dysfunction, T follicular helper (Tfh) cell hyperactivity, and plasmacytoid dendritic cell (pDC) tolerance breakdown. Advances in high-parameter immunophenotyping, single-cell multiomics profiling, and spatial multiomics have redefined SLE pathogenesis, revealing stage-specific immune network perturbations. These discoveries have propelled mechanism-driven therapeutic strategies, including CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy for B cell depletion, disruption of T-B cell synaptic signaling (CD40L inhibitors), and restoration of pDC tolerance (anti-BDCA2 antibodies). While patient heterogeneity poses challenges for universal therapeutic efficacy, emerging strategies integrating molecular endotyping and cellular biomarkers hold promise for overcoming these limitations. By aligning targeted therapies with the immunophenotypic signatures of individual patients, precision medicine approaches are expected to optimize treatment efficacy, minimize off-target effects, and ultimately enhance long-term clinical outcomes in SLE. This review synthesizes current insights into how immune cell perturbations contribute to SLE pathogenesis, modulate disease flares, and determine therapeutic refractoriness, with a critical synthesis of recent clinical trial outcomes.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"73"},"PeriodicalIF":9.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 heterogeneous roles of neutrophils in gastric cancer: scaffold or target?","authors":"Yansong Qin, Yunmei Liu, Peixin Dong, Wen-Bin Zou, Zhaoshen Li, Lei Huang","doi":"10.1186/s11658-025-00744-4","DOIUrl":"10.1186/s11658-025-00744-4","url":null,"abstract":"<p><p>Gastric cancer (GC) is a significant challenge for global health. Neutrophils, the predominant white blood cells in the innate immune system, are increasingly becoming known as potential contributors to either tumor-promoting or tumor-suppressive activities within different tumor biology settings. This review highlights such dual roles of neutrophils in GC, where complex interactions occur within the tumor microenvironment. Specifically, we focus on the formation and function of neutrophil extracellular traps (NETs), which have emerged as critical players in GC progression. NETs influence key processes such as inflammation, angiogenesis, and metastasis. This review offers a comprehensive analysis of the polarization of neutrophils into two of its distinct subtypes, namely N1 and N2, which exert opposing influences on tumor biology. While N1 neutrophils exert anti-tumor properties, N2 neutrophils are generally regarded as pro-tumor. We uniquely discuss how these subtypes interact with cancer cells, affecting epithelial-mesenchymal transition and immune evasion mechanisms. These interactions change the tumor microenvironment and impact overall GC progression. In addition, we underscore the potential of neutrophils and their associated molecules as biomarkers and therapeutic targets. Specific neutrophil-derived markers and neutrophil-associated signaling pathways, along with their perspectives in personalized medicine that would pave the way for neutrophil-based anti-GC therapy, have been discussed in this review. Through the integration of these perspectives, we aim to guide future research involving neutrophils and their therapeutic implications, thus establishing strategies to precisely and effectively treat GC and improve prognosis.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"71"},"PeriodicalIF":9.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 crucial role of metabolic reprogramming in driving macrophage conversion in kidney disease.","authors":"Na Gong, Wenjuan Wang, Yifei Fu, Xumin Zheng, Xinru Guo, Yuhao Chen, Yan Chen, Shengchun Zheng, Guangyan Cai","doi":"10.1186/s11658-025-00746-2","DOIUrl":"10.1186/s11658-025-00746-2","url":null,"abstract":"<p><p>Interstitial fibrosis after acute kidney injury is an ongoing pathological process of chronic inflammatory injury and repair. Macrophages participate in renal inflammation, repair and fibrosis by continuously changing their phenotype and function. The tissue microenvironment of kidney injury induces changes in key metabolic enzymes, pathways and metabolites in macrophages, leading to phenotypic and functional conversions, but the detailed mechanisms are unclear. However, in the early phase of acute kidney injury, macrophages shift to a pro-inflammatory role relying on glycolysis and pentose phosphate pathways. The tissue microenvironment regulates the suppression of glycolysis-related genes and the up-regulation of oxidative phosphorylation and tricarboxylic acid cycle genes in macrophages, resulting in a gradual shift to an anti-inflammatory phenotype, which is involved in tissue repair and remodelling. In the late stage of injury, if macrophages continue to be overactive, they will be involved in renal fibrosis. The concomitant enhancement of nucleotide and amino acid metabolism, especially arginine and glutamine metabolism, is critical for the macrophage function and phenotypic transition during the above injury process. Macrophage metabolic reprogramming therefore provides new therapeutic targets for intervention in inflammatory injury and interstitial fibrosis in kidney disease.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"72"},"PeriodicalIF":9.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 spatiotemporal heterogeneity of reactive oxygen species in the malignant transformation of viral hepatitis to hepatocellular carcinoma: a new insight.","authors":"Huimin Yuan, Jia Liu, Ruochen Xu, Keshan Yang, Ruiyang Qu, Shuai Liu, Yonghui Zhang, Ming Xiang","doi":"10.1186/s11658-025-00745-3","DOIUrl":"10.1186/s11658-025-00745-3","url":null,"abstract":"<p><p>During the transformation of viral hepatitis into hepatocellular carcinoma (HCC), oxidative stress levels increase significantly, leading to tissue damage and chronic inflammation. HCC is characterized by spatiotemporal heterogeneity, which influences oxidative stress patterns, with reactive oxygen species (ROS) as the primary representative molecules. ROS serve not only as critical biomarkers of cancer but also as potential therapeutic targets for HCC, given that their increased levels can either promote or inhibit disease progression. In this review, we systematically examine the temporal heterogeneity of ROS, emphasizing its role in different stages of HCC progression caused by viral hepatitis and in influencing cell fate. We further explore ROS spatial heterogeneity at three levels: cellular, organelle, and biomolecular. Next, we comprehensively review clinical applications and potential therapies designed to selectively modulate ROS on the basis of its spatiotemporal heterogeneity. Finally, we discuss potential future applications of novel therapies that target ROS spatiotemporal heterogeneity to prevent and manage HCC onset and progression. In conclusion, this review enhances understanding of ROS in the progression of viral hepatitis to HCC and offers insights into developing new therapeutic targets and strategies centered on ROS heterogeneity.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"70"},"PeriodicalIF":9.2,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting alveolar macrophages: a promising intervention for pulmonary infection and acute lung injury.","authors":"Fei Hou, Nan Shi, Haoran Yuan, Bingyi Li, Junjie Xiao, Kun Xiao, Lixin Xie","doi":"10.1186/s11658-025-00750-6","DOIUrl":"10.1186/s11658-025-00750-6","url":null,"abstract":"<p><p>Pulmonary infections are common respiratory diseases caused by a variety of pathogens, some of which can lead to epidemics. When they progress to acute lung injury or acute respiratory distress syndrome, the mortality rate is high and effective treatment options are lacking. Macrophages play a crucial role in the development and progression of lung injury, and serve as core components of immune regulation in the lungs. Therefore, regulation of macrophages to intervene in the progression of infection-induced lung injury is a promising research direction. However, the existence of different macrophage subsets and their inherent heterogeneity has led to the failure of many studies to achieve effective results, thereby limiting their clinical applications. We believe that interventions targeting macrophages must consider factors, such as macrophage subsets, timing of interventions, patients' varying immune states, and clinical stages, rather than simply focusing on regulating their phenotypes. This distinction is the key to the success of macrophage-targeted therapies. In this review, we summarize the characteristics of two distinct macrophage subpopulations, lung-tissue-resident alveolar macrophages and monocyte-derived macrophages, along with intervention strategies and research progress at various time points, with the aim of providing insights and directions for future research.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"69"},"PeriodicalIF":9.2,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bypassing the guardian: regulated cell death pathways in p53-mutant cancers.","authors":"Jonathan Y Chung, Bruce A Knutson","doi":"10.1186/s11658-025-00751-5","DOIUrl":"10.1186/s11658-025-00751-5","url":null,"abstract":"<p><p>Approximately half of all cancers bear mutations in the tumor suppressor p53. Despite decades of research studying p53 function, treatment of p53-mutant cancers remains challenging owing to the effects of p53 mutations on many complex and interrelated signaling networks that promote tumor metastasis and chemoresistance. Mutations in p53 promote tumor survival by dysregulating cellular homeostasis and preventing activation of regulated cell death (RCD) pathways, which normally promote organismal health by eliminating dysregulated cells. Activation of RCD is a hallmark of effective cancer therapies, and p53-mutant cancers may be particularly susceptible to activation of certain RCD pathways. In this review, we discuss four RCD pathways that are the targets of emerging cancer therapeutics to treat p53-mutant cancers. These RCD pathways include E2F1-dependent apoptosis, necroptosis, mitochondrial permeability transition-driven necrosis, and ferroptosis. We discuss mechanisms of RCD activation, effects of p53 mutation on RCD activation, and current pharmaceutical strategies for RCD activation in p53-mutant cancers.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"68"},"PeriodicalIF":10.2,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CIP2A promotes inflammation and exacerbates osteoarthritis by targeting CEMIP.","authors":"Jingyue Su, Xuying Sun, Xin Chen, Kang Wei, Danni Luo, Shengwu Yang, Chunwu Zhang, Jian Xu, Zhenhan Deng","doi":"10.1186/s11658-025-00748-0","DOIUrl":"10.1186/s11658-025-00748-0","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) is a chronic joint disease characterized by cartilage degeneration with unclear pathogenic mechanism. This study aims to discuss the regulatory role of cancerous inhibitor of protein phosphatase 2A (CIP2A) in OA pathogenesis and to elucidate the molecular mechanisms.</p><p><strong>Methods: </strong>Mouse chondrocytes were induced by interleukin-1β (IL-1β) to mimic OA inflammation, and extracellular matrix (ECM) homeostasis and inflammatory factors were evaluated at mRNA and protein levels. A mouse model of OA was induced by destabilization of medial meniscus (DMM) surgery. Histopathological staining was used to assess the cartilage destruction of human and mouse. Osteophyte formation was observed using micro-computed tomography (CT). Downstream of CIP2A was screened by RNA sequencing and coimmunoprecipitation coupled with mass spectrometry in mouse chondrocytes.</p><p><strong>Results: </strong>CIP2A was downregulated in cartilage of patients with OA and DMM mouse models, as well as in IL-1β-induced mouse chondrocytes. However, CIP2A overexpression promoted ECM degradation and inflammatory processes and exacerbated cartilage destruction and osteophyte formation. By contrast, knockdown or pharmacological inhibition of CIP2A alleviated cartilage degeneration to a certain extent, with no improvement in osteophytes formation caused by OA. Mechanistically, CIP2A interacted with its downstream cell migration-inducing protein (CEMIP) and activated the nuclear factor kappa B (NF-κB) signaling pathway, resulting in the imbalance of cartilage anabolic and catabolic factors and the activation of inflammation in the development of OA. In addition, CIP2A was ubiquitinated in mouse chondrocytes, causing it to be degraded, which could be a negative feedback of CIP2A expression in OA.</p><p><strong>Conclusions: </strong>CIP2A targets CEMIP to activate NF-κB signaling pathway, which in turn aggravates cartilage destruction and inflammation and ultimately accelerates OA development. Our results suggest the potential role of the CIP2A/CEMIP axis as a therapeutic target for OA.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"67"},"PeriodicalIF":9.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular signatures of disulfidptosis: interplay with programmed cell death pathways and therapeutic implications in oncology.","authors":"Yingchao Liu, Sainan Li, Yunyi Wu, Ping Zhang, Yanhua Yu, Xi Chen, Lingyan Yu, Xinyi Yang, Huanjuan Li, Cuiyun Wu, Jing Du, Yanchun Li","doi":"10.1186/s11658-025-00743-5","DOIUrl":"10.1186/s11658-025-00743-5","url":null,"abstract":"<p><p>Disulfidptosis represents a newly identified form of regulated cell death (RCD) distinct from other well-established RCD pathways. It occurs during periods of glucose starvation, specifically when intracellular NADPH is rapidly depleted and the expression of Solute Carrier Family 7 Member 11 (SLC7A11) is highly upregulated. Cancer cells utilize SLC7A11 to import cystine from the extracellular environment, and subsequently employ NADPH to convert it into cysteine. In the event of NADPH deficiency or an impairment in its utilization, cystine accumulates within the cells. This accumulation results in abnormal disulfide bond formation within actin cytoskeleton proteins, which in turn causes the collapse of the actin network and ultimately triggers disulfidptosis. This process uncovers a metabolic vulnerability within tumors, offering novel perspectives on the mechanisms that underlie cell death. In this paper, we provide a comprehensive review of the mechanism of disulfidptosis and compare its similarities and differences with other common programmed cell death mechanisms, such as apoptosis, autophagy, ferroptosis, and cuproptosis. The aim is to gain a more profound understanding of the characteristics and mechanisms of various cell death pathways. Understanding the correlation between disulfidptosis and tumors constitutes a crucial theoretical foundation for future research endeavors in cancer treatment. This review offers valuable insights that could pave the way for developing novel cancer treatment strategies and lead to groundbreaking advancements in cancer therapy.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"66"},"PeriodicalIF":9.2,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FNDC3B promotes gastric cancer metastasis via interacting with FAM83H and preventing its proteasomal degradation.","authors":"Yuying Zhang, Lingyu Ran, Yuying Liu, Wei Li, Ai Ran, Haiping Li, Bo Huang, Junwu Ren, Hao Ning, Qiang Ma, Xiaolin Wang, Feifei Yang, Xiaojuan Pan, Ce Liang, Shimin Wang, Changhong Qin, Yan Jiang, Kun Qian, Bin Xiao","doi":"10.1186/s11658-025-00741-7","DOIUrl":"10.1186/s11658-025-00741-7","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is one of the most prevalent digestive tract malignancies, with metastasis being a major contributor to poor prognosis in patients. Fibronectin type III domain-containing 3B (FNDC3B) plays pivotal roles in various tumors, yet its role in GC remains unknown.</p><p><strong>Methods: </strong>We utilized a GC immunohistochemistry (IHC) chip and specimens to identify high expression of FNDC3B in GC. In vitro cellular experiments and in vivo nude mouse models were constructed to validate the biological functions of FNDC3B. Truncated mutants of FNDC3B and immunofluorescence (IF) assays were conducted to explore the critical domains of FNDC3B. Liquid chromatography-tandem mass spectrometry (LC-MS) and coimmunoprecipitation (Co-IP) were employed to screen and identify target proteins interacting with FNDC3B. Rescue experiments were performed to uncover interactions between FNDC3B and the binding protein.</p><p><strong>Results: </strong>FNDC3B was found to function as an oncogene in GC. Clinically, FNDC3B was significantly upregulated in GC specimens and associated with poor survival in patients with GC. Functionally, elevated FNDC3B promoted GC metastasis both in vitro and in vivo. Structurally, the proline-rich N-terminus and a transmembrane (TM) domain at the C-terminus were crucial for maintaining the metastasis function of FNDC3B. Mechanistically, FNDC3B interacted with FAM83H, inhibiting the ubiquitin-proteasome degradation of FAM83H, which in turn enhanced GC progression through the FNDC3B/FAM83H/Snail/EMT axis.</p><p><strong>Conclusions: </strong>Our results demonstrate that FNDC3B promotes GC metastasis and has the potential to serve as a therapeutic target for GC.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"65"},"PeriodicalIF":9.2,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YAP1 promoter-associated noncoding RNA affects Ewing sarcoma cell tumorigenicity by regulating YAP1 expression.","authors":"Lidia Chellini, Arianna Del Verme, Veronica Riccioni, Maria Paola Paronetto","doi":"10.1186/s11658-025-00736-4","DOIUrl":"10.1186/s11658-025-00736-4","url":null,"abstract":"<p><strong>Background: </strong>Ewing sarcomas (ESs) are aggressive paediatric tumours of bone and soft tissues afflicting children and adolescents. Despite current therapies having improved the 5-year survival rate to 70% in patients with localized disease, 25% of patients relapse and most have metastasis at diagnosis. Resistance to chemotherapy, together with the high propensity to metastasize, remain the main causes of treatment failure. Thus, identifying novel targets for alternative therapeutic approaches is urgently needed.</p><p><strong>Methods: </strong>Biochemical and functional analyses were carried out to elucidate the mechanism of regulation of YAP1 expression by pncRNA_YAP1-1 in ES cells.</p><p><strong>Results: </strong>Here, we identified a novel promoter-associated noncoding RNA, pncRNA_YAP1-1, transcribed from the YAP1 promoter in ES cells. We found that pncRNA_YAP1-1 level exerts antitumour effects on ES by destabilizing YAP1 protein. The molecular mechanism relies on the interaction of pncRNA_YAP1-1 with the RNA binding protein FUS, which stabilizes the transcript. Furthermore, pncRNA_YAP1-1 binding to TEAD impairs its interaction with YAP1, thus determining YAP1 translocation into the cytoplasm, its phosphorylation and degradation.</p><p><strong>Conclusions: </strong>Overall, our findings reveal a novel layer of regulation of YAP1 protein expression by pncRNA_YAP1-1 in Ewing sarcoma. Considering the role of YAP1 in therapy response and cell propensity to metastasize, our results indicate pncRNA_YAP1-1 as an actionable target that could be exploited to enhance chemotherapy efficacy in Ewing sarcoma.</p><p><strong>Significance: </strong>PncRNA_YAP1-1 counteracts the YAP1 oncogenic transcriptional program in Ewing sarcoma cells by interfering with YAP1-TEAD interaction and impairing YAP1 protein stability. These findings uncover a novel treatment option for Ewing sarcoma.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"63"},"PeriodicalIF":9.2,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}