Apoptosis最新文献_第4页

Machine learning-based integration reveals immunological heterogeneity and the clinical potential of T cell receptor (TCR) gene pattern in hepatocellular carcinoma 基于机器学习的整合揭示了肝细胞癌中 T 细胞受体 (TCR) 基因模式的免疫异质性和临床潜力。

IF 6.1 2区生物学

Apoptosis Pub Date : 2025-02-04 DOI: 10.1007/s10495-025-02080-6

Zewei Zhuo, Huihuan Wu, Lingli Xu, Yuran Ji, Jiezhuang Li, Liehui Liu, Hong Zhang, Qi Yang, Zhongwen Zheng, Weijian Lun

{"title":"Machine learning-based integration reveals immunological heterogeneity and the clinical potential of T cell receptor (TCR) gene pattern in hepatocellular carcinoma","authors":"Zewei Zhuo, Huihuan Wu, Lingli Xu, Yuran Ji, Jiezhuang Li, Liehui Liu, Hong Zhang, Qi Yang, Zhongwen Zheng, Weijian Lun","doi":"10.1007/s10495-025-02080-6","DOIUrl":"10.1007/s10495-025-02080-6","url":null,"abstract":"<div><p>The T Cell Receptor (TCR) significantly contributes to tumor immunity, whereas the intricate interplay with the Hepatocellular Carcinoma (HCC) microenvironment and clinical significance remains largely unexplored. Here, we aimed to examine the function of TCR signaling in tumor immunity and its clinical significance in HCC. Our objective was to employ TCR signaling genes and a machine learning-based integrative methodology to construct a prognostic prediction system termed the TCR score. Herein, we revealed that the TCR score serves as an independent risk factor for overall survival in HCC patients, demonstrating stable and robust performance. The accuracy of the TCR score significantly exceeds that of traditional clinical variables and published signatures. Additionally, the immune infiltration was abundant in patients with low TCR scores. Single-cell cohort analysis further demonstrates that patients with low TCR scores possess an immune-active tumor microenvironment (TME), with T/NK cells enhancing interactions with myeloid cells through signaling networks such as MIF, MK, and SPP1. In response to these changes in the TME, patients with high TCR scores exhibit poorer outcomes and shorter survival in immunotherapy cohorts. In vitro experiments demonstrated that the key TCR signaling biomarker SOS1 knockdown significantly suppresses the HCC cells’ capability to proliferate, invade, and migrate while enhancing tumor cell apoptosis. The TCR score could function as a robust and potential tool to predict immune activity and improve clinical outcomes for HCC patients.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 3-4","pages":"955 - 975"},"PeriodicalIF":6.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Silencing LINC01547 induces hepatocellular carcinoma cell apoptosis and metastasis inhibition via the ADAR1/FAK and miR-146b-5p/RAC1 axes 沉默LINC01547可通过ADAR1/FAK和miR-146b-5p/RAC1轴诱导肝癌细胞凋亡并抑制转移。

IF 6.1 2区生物学

Apoptosis Pub Date : 2025-02-04 DOI: 10.1007/s10495-024-02070-0

Dan Wang, Huijie Zhao, Ying Zhao, Xuejing An, Chuanqin Shi, Zhaohai Pan, Qiusheng Zheng, Xin Wang, Jun Lu, Defang Li

{"title":"Silencing LINC01547 induces hepatocellular carcinoma cell apoptosis and metastasis inhibition via the ADAR1/FAK and miR-146b-5p/RAC1 axes","authors":"Dan Wang, Huijie Zhao, Ying Zhao, Xuejing An, Chuanqin Shi, Zhaohai Pan, Qiusheng Zheng, Xin Wang, Jun Lu, Defang Li","doi":"10.1007/s10495-024-02070-0","DOIUrl":"10.1007/s10495-024-02070-0","url":null,"abstract":"<div><p>Growing research indicates that long noncoding RNAs (lncRNAs) are pivotal in the development and advancement of hepatocellular carcinoma (HCC). Our research pinpointed LINC01547 as a notable lncRNA that was significantly downregulated in Hep3B cells treated with bufotalin, whereas it exhibited elevated expression levels in HCC tumor tissues. Further study found that silencing LINC01547 markedly suppressed proliferation, induced apoptosis, and inhibited migration and invasion in Hep3B and HepG2 cells. LINC01547 knockdown reduced ADAR1 expression, which led to apoptosis and suppressed metastasis via inhibition of the FAK signaling pathway. Additionally, silencing LINC01547 upregulated miR-146b-5p, which in turn decreased RAC1 levels, further promoting apoptosis and inhibiting metastasis in HCC cells. In vivo, a Hep3B tumor-bearing mouse model confirmed the antitumor effects of LINC01547 silencing. Our findings demonstrate that LINC01547 regulates HCC cell apoptosis and metastasis through the ADAR1/FAK and miR-146b-5p/RAC1 pathways, suggesting that LINC01547 may serve as a biomarker and potential therapeutic target for HCC.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 3-4","pages":"936 - 954"},"PeriodicalIF":6.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeted editing of CCL5 with CRISPR-Cas9 nanoparticles enhances breast cancer immunotherapy

IF 6.1 2区生物学

Apoptosis Pub Date : 2025-01-27 DOI: 10.1007/s10495-024-02032-6

Wei Yan, Shuo Wang, Lihui Zhu, Xinlin Yu, Jianglong Li

{"title":"Targeted editing of CCL5 with CRISPR-Cas9 nanoparticles enhances breast cancer immunotherapy","authors":"Wei Yan, Shuo Wang, Lihui Zhu, Xinlin Yu, Jianglong Li","doi":"10.1007/s10495-024-02032-6","DOIUrl":"10.1007/s10495-024-02032-6","url":null,"abstract":"<div><p>Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide. Immunotherapy, a promising therapeutic approach, often faces challenges due to the immunosuppressive tumor microenvironment. This study explores the innovative use of CRISPR-Cas9 technology in conjunction with FCPCV nanoparticles to target and edit the C-C Motif Chemokine Ligand 5 (CCL5) gene, aiming to improve the efficacy of breast cancer immunotherapy. Single-cell RNA sequencing (scRNA-seq) and TCGA-BRCA data identified CCL5 as a key immune-related gene in breast cancer. Using CRISPR-Cas9, sgRNA targeting CCL5 was designed and delivered to breast cancer cells and humanized mouse models via FCPCV nanoparticles. In vitro experiments demonstrated that FCPCV nanoparticles effectively silenced CCL5, enhanced CD8<sup>+</sup> T cell activity, and increased the production of cytokines such as IFN-γ, TNF-α, and GZMB. In vivo studies revealed significant tumor suppression, improved immune microenvironment, and increased CD8<sup>+</sup>/CD4<sup>+</sup> ratios in treated mice, without notable toxic side effects. These findings highlight the potential of CRISPR-Cas9 nanoparticle-mediated gene editing as a novel strategy for enhancing breast cancer immunotherapy, providing a new direction for personalized and effective cancer treatment.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 3-4","pages":"912 - 935"},"PeriodicalIF":6.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-024-02032-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051412","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}

引用次数: 0

sVEGFR3 alleviates myocardial ischemia/reperfusion injury through regulating mitochondrial homeostasis and immune cell infiltration

IF 6.1 2区生物学

Apoptosis Pub Date : 2025-01-25 DOI: 10.1007/s10495-024-02068-8

Liqun Shang, Yuanhan Ao, Xiaolin Huang, Huawei Wu, Kangni Feng, Junjie Wang, Yuan Yue, Zhuoming Zhou, Quan Liu, Huayang Li, Guangguo Fu, Kaizheng Liu, Jinyu Pan, Yang Huang, Jiantao Chen, Guangxian Chen, Mengya Liang, Jianping Yao, Suiqing Huang, Jian Hou, Zhongkai Wu

{"title":"sVEGFR3 alleviates myocardial ischemia/reperfusion injury through regulating mitochondrial homeostasis and immune cell infiltration","authors":"Liqun Shang, Yuanhan Ao, Xiaolin Huang, Huawei Wu, Kangni Feng, Junjie Wang, Yuan Yue, Zhuoming Zhou, Quan Liu, Huayang Li, Guangguo Fu, Kaizheng Liu, Jinyu Pan, Yang Huang, Jiantao Chen, Guangxian Chen, Mengya Liang, Jianping Yao, Suiqing Huang, Jian Hou, Zhongkai Wu","doi":"10.1007/s10495-024-02068-8","DOIUrl":"10.1007/s10495-024-02068-8","url":null,"abstract":"<div><p>Recent studies have suggested that sVEGFR3 is involved in cardiac diseases by regulating lymphangiogenesis; however, results are inconsistent. The aim of this study was to investigate the function and mechanism of sVEGFR3 in myocardial ischemia/reperfusion injury (MI/RI). sVEGFR3 effects were evaluated in vivo in mice subjected to MI/RI, and in vitro using HL-1 cells exposed to oxygen-glucose deprivation/reperfusion. Echocardiography, TTC-Evans blue staining, ELISA, electron microscopy, immunofluorescence, western blotting, and flow cytometry were used to investigate whether sVEGFR3 attenuates I/R injury. Transcriptome sequencing was used to investigate the downstream mechanism of sVEGFR3. Results showed that, in vivo, sVEGFR3 pretreatment reduced cardiac dysfunction, infarct area, and myocardial injury indicators by reducing ROS production, AIF expression, and apoptosis. In vitro, sVEGFR3 restored mitochondrial homeostasis by stabilizing the mitochondrial membrane potential (MMP) and preventing the opening of mitochondrial permeability transition pores (mPTP). And sVEGFR3 inhibits mitochondrial apoptosis through the Ras/MEK/ERK pathway. Furthermore, I/R injury increased the proportion of M1 macrophages and CD4 + T cells in myocardial tissue, as well as serum IFN-γ and TNF-α levels, whereas sVEGFR3 treatment attenuated these effects. sVEGFR3 attenuates MI/RI by regulating mitochondrial homeostasis and immune cell infiltration, and reduces intrinsic ROS-mediated mitochondrial apoptosis via the Ras/MEK/ERK pathway.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 3-4","pages":"894 - 911"},"PeriodicalIF":6.1,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanisms of apoptosis-related non-coding RNAs in ovarian cancer: a narrative review 卵巢癌中凋亡相关非编码rna的机制：综述。

IF 6.1 2区生物学

Apoptosis Pub Date : 2025-01-20 DOI: 10.1007/s10495-024-02074-w

Yue Wang, Shirui Wang, Haiyan He, Yingying Bai, Zhuo Liu, Sima-Sadat Sabihi

{"title":"Mechanisms of apoptosis-related non-coding RNAs in ovarian cancer: a narrative review","authors":"Yue Wang, Shirui Wang, Haiyan He, Yingying Bai, Zhuo Liu, Sima-Sadat Sabihi","doi":"10.1007/s10495-024-02074-w","DOIUrl":"10.1007/s10495-024-02074-w","url":null,"abstract":"<div><p>Ovarian cancer remains a major challenge in oncology due to its complex biology and late-stage diagnosis. Recent advances in molecular biology have highlighted the crucial role of non-coding RNAs (ncRNAs) in regulating apoptosis and cancer progression. NcRNAs, including microRNAs, long non-coding RNAs, and circular RNAs, have emerged as significant players in the molecular networks governing ovarian cancer. Despite these insights, the precise mechanisms by which ncRNAs influence ovarian cancer pathology are not fully understood. This complexity, combined with the heterogeneity of the disease and the development of treatment resistance, poses substantial obstacles to effective therapeutic development. Additionally, the lack of reliable early detection methods further complicates treatment strategies. This manuscript reviews the current state of research on ncRNAs in ovarian cancer, discusses the challenges in translating these findings into clinical applications, and outlines potential future directions. Emphasis is placed on the need for integrated approaches to unravel the intricate roles of ncRNAs, improve early detection, and develop personalized treatment strategies to address the diverse and evolving nature of ovarian cancer. While these findings provide valuable insights, it is crucial to recognize that many results are based on preclinical studies and require further validation to establish their clinical applicability.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 3-4","pages":"553 - 578"},"PeriodicalIF":6.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Emerging role of PANoptosis in kidney diseases: molecular mechanisms and therapeutic opportunities PANoptosis在肾脏疾病中的新作用：分子机制和治疗机会。

IF 6.1 2区生物学

Apoptosis Pub Date : 2025-01-20 DOI: 10.1007/s10495-024-02072-y

Yi Hou, Qi Feng, Cien Wei, Fengyu Cao, Dongwei Liu, Shaokang Pan, Yan Shi, Zhangsuo Liu, Fengxun Liu

{"title":"Emerging role of PANoptosis in kidney diseases: molecular mechanisms and therapeutic opportunities","authors":"Yi Hou, Qi Feng, Cien Wei, Fengyu Cao, Dongwei Liu, Shaokang Pan, Yan Shi, Zhangsuo Liu, Fengxun Liu","doi":"10.1007/s10495-024-02072-y","DOIUrl":"10.1007/s10495-024-02072-y","url":null,"abstract":"<div><p>Kidney diseases represent a significant global public health challenge, characterized by complex pathogenesis, high incidence, low awareness, insufficient early screening, and substantial treatment disparities. Effective therapeutic options remain lacking. Programmed cell death (PCD), including apoptosis, pyroptosis, and necroptosis, play pivotal roles in the pathogenesis of various kidney diseases. In 2019, PANoptosis, a novel form of inflammatory cell death, was introduced, providing new insights into innate immunity and PCD research. Although research on PANoptosis in kidney diseases is still limited, identifying key molecules within PANoptosomes and understanding their regulatory roles is critical for disease prevention and management. This review summarizes the various forms of PCD implicated in kidney diseases, along with PANoptosomes activated by Z-DNA binding protein 1 (ZBP1), absent in melanoma 2 (AIM2), receptor-interacting protein kinase 1 (RIPK1), NOD-like receptor family CARD domain containing 12 (NLRP12), and NOD-like receptor family member C5 (NLRC5). It also reviews the advancements in PANoptosis research in the field of kidney diseases, particularly in renal tumors and acute kidney injuries (AKI). The goal is to establish a foundation for future research into the role of PANoptosis in kidney diseases.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 3-4","pages":"579 - 596"},"PeriodicalIF":6.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Silibinin’s role in counteracting neuronal apoptosis and synaptic dysfunction in Alzheimer’s disease models 水飞蓟宾在阿尔茨海默病模型中对抗神经元凋亡和突触功能障碍的作用。

IF 6.1 2区生物学

Apoptosis Pub Date : 2025-01-20 DOI: 10.1007/s10495-024-02073-x

Baohui Zhang, Di Zhang, Keyan Chen, Tengfei Wu

{"title":"Silibinin’s role in counteracting neuronal apoptosis and synaptic dysfunction in Alzheimer’s disease models","authors":"Baohui Zhang, Di Zhang, Keyan Chen, Tengfei Wu","doi":"10.1007/s10495-024-02073-x","DOIUrl":"10.1007/s10495-024-02073-x","url":null,"abstract":"<div><p>This study investigates silibinin’s capacity to mitigate Alzheimer’s disease (AD) pathologies with a particular emphasis on its effects on apoptosis and synaptic dysfunction in AD models. Employing APP/PS1 transgenic mice and SH-SY5Y neuroblastoma cell lines, our research assessed the efficacy of silibinin in reducing amyloid-beta (Aβ) deposition, neuroinflammation, and neuronal apoptosis. Our results demonstrate that silibinin significantly decreases Aβ accumulation and neuroinflammation and robustly inhibits apoptosis in neuronal cells. Additionally, silibinin enhances the expression of synaptic proteins, thereby supporting synaptic integrity. Through network pharmacology analysis, we identified potential targets of silibinin in Aβ metabolism and synaptic functions. Mechanistically, our findings suggest that silibinin promotes neuronal survival predominantly via the modulation of the Fyn/GluN2B/CaMKIIα signaling pathway, which protects against Aβ1-42-induced apoptosis. These insights highlight silibinin’s potential as a therapeutic agent for AD, particularly its role in reducing neuronal apoptosis and maintaining synaptic function.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 3-4","pages":"861 - 879"},"PeriodicalIF":6.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Combined effects of natural products and exercise on apoptosis pathways in obesity-related skeletal muscle dysfunction 天然产物和运动对肥胖相关骨骼肌功能障碍细胞凋亡途径的联合影响。

IF 6.1 2区生物学

Apoptosis Pub Date : 2025-01-20 DOI: 10.1007/s10495-024-02069-7

Chun Pan, Yiying Yang, Zailin Zhao, Jingye Hu

{"title":"Combined effects of natural products and exercise on apoptosis pathways in obesity-related skeletal muscle dysfunction","authors":"Chun Pan, Yiying Yang, Zailin Zhao, Jingye Hu","doi":"10.1007/s10495-024-02069-7","DOIUrl":"10.1007/s10495-024-02069-7","url":null,"abstract":"<div><p>Obesity and related metabolic disorders are closely linked to increased apoptosis in skeletal muscle, leading to muscle degeneration, insulin resistance, and the progression of diseases such as type 2 diabetes and sarcopenia. This review explores the combined effects of natural products, including resveratrol, curcumin, and quercetin, and physical exercise on modulating apoptosis pathways in skeletal muscle. Both natural products and regular physical activity independently reduce oxidative stress and improve mitochondrial function, thereby regulating the balance between pro-apoptotic and anti-apoptotic signals. When combined, these interventions amplify their protective effects on muscle health, promoting mitochondrial biogenesis, reducing apoptosis, and enhancing muscle regeneration. This review also discusses the molecular mechanisms by which these strategies influence apoptosis, with a focus on the Bcl-2 pathway, and explores the clinical implications for the prevention and treatment of obesity-related diseases. The synergistic benefits of combining exercise with natural product supplementation offer a promising therapeutic approach for managing metabolic disorders, preserving muscle function, and improving overall metabolic health.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 3-4","pages":"537 - 552"},"PeriodicalIF":6.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-024-02069-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998865","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}

引用次数: 0

Programmed cardiomyocyte death in myocardial infarction 心肌梗死中的程序性心肌细胞死亡。

IF 6.1 2区生物学

Apoptosis Pub Date : 2025-01-20 DOI: 10.1007/s10495-025-02075-3

Hao Wu, Qi Lan, Yi-Xiang He, Jin-Yi Xue, Hao Liu, Yuan Zou, Ping Liu, Gang Luo, Ming-Tai Chen, Meng-Nan Liu

引用次数: 0

Exosomes derived from FN14-overexpressing BMSCs activate the NF-κB signaling pathway to induce PANoptosis in osteosarcoma 来自过表达fn14的骨髓间充质干细胞的外泌体激活NF-κB信号通路，诱导骨肉瘤PANoptosis。

IF 6.1 2区生物学

Apoptosis Pub Date : 2025-01-20 DOI: 10.1007/s10495-024-02071-z

Liangming Wang, Yanbin Huang, Xiaolu Zhang, Wenkai Chen, Zhangsheng Dai

{"title":"Exosomes derived from FN14-overexpressing BMSCs activate the NF-κB signaling pathway to induce PANoptosis in osteosarcoma","authors":"Liangming Wang, Yanbin Huang, Xiaolu Zhang, Wenkai Chen, Zhangsheng Dai","doi":"10.1007/s10495-024-02071-z","DOIUrl":"10.1007/s10495-024-02071-z","url":null,"abstract":"<div><p>Despite advances in treatment, the prognosis of osteosarcoma (OS) patients is unsatisfactory, and searching for possible targets is substantial. Fibroblast growth factor inducible type 14 (FN14), a plasma membrane protein, is involved in wound healing, angiogenesis, proliferation, apoptosis, and inflammation. However, its implication in OS development and progression has not been completely characterized. Herein, we explored the cell-to-cell communication of bone marrow mesenchymal stem cells (BMSCs) and OS cells mediated by FN14 in the tumor microenvironment of OS. To assess the interplay between FN14 expression levels and patient survival, FN14 expression was measured in both normal and OS tissues. The FN14 overexpressing BMSCs (OE) were constructed using lentivirus, and exosomes (EXO) were extracted. The uptake of FN14-containing EXO by OS cells was analyzed via flow cytometry and in vivo fluorescence imaging. In addition, high-throughput sequencing was performed to analyze the mechanisms by which EXO inhibits OS cell growth. Finally, the therapeutic effect of OE-EXO was evaluated in a mouse model of OS xenografts. The results showcased reduced FN14 expression in human and mouse OS tissues, suggesting its role may be involved in the malignant progression of OS. The FN14 expression was higher in BMSCs relative to OS cells, and FN14 was secreted and excreted by EXO. The OS cell progression was suppressed after the uptake of FN14-derived EXO from BMSCs. In addition, RNA sequencing revealed that FN14 in EXO activated NF-κB signaling, triggering PANoptosis in OS cells. In vivo, OE-EXO injection inhibited tumor growth in OS xenografts and significantly improved the long-term survival of mice. Our findings suggest that FN14 carried by EXO from BMSCs activates the NF-κB pathway to trigger PANoptosis in OS cells, providing a potential therapeutic strategy to inhibit OS progression.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 3-4","pages":"880 - 893"},"PeriodicalIF":6.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-024-02071-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998886","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}

引用次数: 0