Apoptosis最新文献

{"title":"Single-cell RNA sequencing analysis reveals the dynamic changes in the tumor microenvironment during NMIBC recurrence.","authors":"Ziang Chen, Tianxiang Zhang, Weijian Li, Jia Hu, Yuxi Ou, Fangdie Ye, Jinhao Zhang, Haowen Jiang, Shenghua Liu","doi":"10.1007/s10495-024-02044-2","DOIUrl":"https://doi.org/10.1007/s10495-024-02044-2","url":null,"abstract":"<p><strong>Background: </strong>Due to the clinical characteristic of frequent recurrence in urothelial bladder cancer (UBC), patients face significant health impacts and economic burdens. Therefore, understanding the molecular mechanisms involved in UBC recurrence is crucial for reducing its recurrence rate. The aim of our study is to help urologists and clinical researchers gain a deeper understanding of the changes in the tumor microenvironment (TME) during UBC recurrence.</p><p><strong>Methods: </strong>We collected 10 samples from primary and recurrent non-muscle-invasive bladder cancer (NMIBC) and performed single-cell RNA sequencing. By distinguishing and annotating cell subpopulations, we identified tissue preferences of some novel cell subgroups. Next, pseudotime trajectory analysis, cell-cell communication analysis, and function enrichment analysis were applied to evaluate the dynamic changes in the TME and biological functions. Finally, we validated the distribution of some of these cell subgroups using multiplex immunofluorescence experiments.</p><p><strong>Results: </strong>We identified a tumor-associated fibroblast (CAF) subtype with high COL18A1 expression that is highly expressed in recurrent NMIBC, suggesting that the stromal component of the tumor may play a crucial role in the recurrence process. Additionally, pseudotime trajectory analysis revealed a macrophage subtype with high IL-6 expression at the terminal stage of macrophage differentiation, exhibiting significant immunosuppressive features. This indicated the presence of immune exhaustion during NMIBC recurrence. Lastly, we found an upregulation of estrogen in recurrent urothelial cancer cells, which may partially explain the gender disparity observed in UBC.</p><p><strong>Conclusion: </strong>This study identified several cell subpopulations influencing NMIBC recurrence, which were heavily infiltrated in the TME of recurrent NMIBC. Additionally, the enrichment of estrogen in urothelial cancer cells from various sources suggested a role of sex hormones in NMIBC recurrence.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779080","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}

{"title":"Integrated explainable machine learning and multi-omics analysis for survival prediction in cancer with immunotherapy response.","authors":"Alphonse Houssou Hounye, Li Xiong, Muzhou Hou","doi":"10.1007/s10495-024-02050-4","DOIUrl":"https://doi.org/10.1007/s10495-024-02050-4","url":null,"abstract":"<p><p>To demonstrate the efficacy of machine learning models in predicting mortality in melanoma cancer, we developed an interpretability model for better understanding the survival prediction of cancer. To this end, the optimal features were identified, ten different machine learning models were utilized to predict mortality across various datasets. Then we have utilized the important features identified by those machines learning methods to construct a new model named NKECLR to forecast mortality of patient with cancer. To explicitly clarify the model's decision-making process and uncover novel findings, an interpretable technique incorporating machine learning and SHapley Additive exPlanations (SHAP), as well as LIME, has been employed, and four genes EPGN, PHF11, RBM34, and ZFP36 were identified from those machine learning(ML). The experimental analysis conducted on training and validation datasets demonstrated that the proposed model has a good performance com- pared to existing methods with AUC value 81.8%, and 79.3%, respectively. Moreover, when combined our NKECLR with PD-L1, PD-1, and CTLA-4 the AUC value was 83%0. Finally, these findings have been applied to comprehend the response of drugs and immunotherapy. Our research introduced an innovative predictive NKECLR model utilizing natural killer(NK) cell marker genes for cohorts with melanoma cancer. The NKECLR model can effectively predict the survival of melanoma cancer cohorts and treatment results, revealing distinct immune cell infiltration in the high-risk group.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779137","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}

{"title":"The N6-methyladenosine writer METTL3 promotes breast cancer progression through YTHDF2-dependent posttranscriptional silencing of GSDMD.","authors":"You Shuai, Zhonghua Ma, Jie Ju, Chunxiao Li, Xiaorong Bai, Jian Yue, Xue Wang, Peng Yuan, Haili Qian","doi":"10.1007/s10495-024-02037-1","DOIUrl":"https://doi.org/10.1007/s10495-024-02037-1","url":null,"abstract":"<p><p>Cell pyroptosis is a form of programmed cell death, with Gasdermin-D (GSDMD) acting as its key executor. While activating pyroptosis represents a promising therapeutic strategy for cancer, the regulatory mechanisms governing GSDMD expression during cell death remain poorly understood. In this study, we identified METTL3 as a negative regulator of GSDMD-mediated pyroptosis, with high expression in breast cancer (BC) cells. YTHDF2 was found to recognize the m6A modification of GSDMD, thereby decreasing its stability. Finally, in vivo experiments further demonstrated the inhibitory effect of the METTL3 inhibitor STM2457 on tumors. Overall, these findings suggest that inhibition of METTL3 can enhance GSDMD-mediated pyroptosis and reveal a novel regulatory mechanism governing GSDMD expression, presenting a novel strategy for cancer treatment.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765847","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}

{"title":"The gut microbial metabolite phenylacetylglutamine increases susceptibility to atrial fibrillation after myocardial infarction through ferroptosis and NLRP3 inflammasome.","authors":"Guangji Wang, Qin He, Wei Shuai, Hongjie Yang, Bin Kong, Shimin Lu, Yang Gong","doi":"10.1007/s10495-024-02046-0","DOIUrl":"https://doi.org/10.1007/s10495-024-02046-0","url":null,"abstract":"<p><p>Myocardial infarction (MI) is an important risk factor for the development of atrial fibrillation (AF), and the gut microbial metabolite phenylacetylglutamine (PAGln) is strongly associated with the prognosis of MI patients. However, whether PAGln is involved in the regulation of AF after MI is currently unknown. Therefore, the present study aimed to explore the effect of PAGln on the susceptibility to AF after MI. MI model was constructed by surgically ligating the left anterior descending branch of the coronary artery. PAGln was administered by intraperitoneal injection for 7 consecutive days starting after surgery and then investigated by histopathologic, molecular biological, and electrophysiologic studies. Myocardial ischemia resulted in intestinal barrier dysfunction and significantly increased circulating levels of PAGln. Compared with the myocardial ischemia group, administration of PAGln significantly exacerbated atrial fibrosis and atrial electrical remodeling in mice after myocardial ischemia, as evidenced by shortening of the ERP (at varying pacing cycle lengths of 40, 60, 80, and 100), ion channel remodeling (Nav1.5, Cav1.2, and Kv1.5), and decreased expression of CX40, which led to an increase in the susceptibility to AF (54.5% vs. 90.9%, P < 0.05). In addition, administration of PAGln further exacerbated MI-induced intestinal barrier dysfunction compared with the MI group. Mechanistically, PAGln may affect atrial remodeling and AF susceptibility after MI by modulating ferroptosis and NLRP3 inflammasome. The present study preliminarily reveals that the gut microbial metabolite PAGln exacerbates post-MI AF remodeling and AF susceptibility, possibly through ferroptosis and activation of NLRP3 inflammasome.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765845","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}

{"title":"Golgi-derived extracellular vesicle production induced by SARS-CoV-2 envelope protein.","authors":"Qiguang Li, Qian Liu, Shuangqu Li, Xiaoli Zuo, Hu Zhou, Zhaobing Gao, Bingqing Xia","doi":"10.1007/s10495-024-02035-3","DOIUrl":"https://doi.org/10.1007/s10495-024-02035-3","url":null,"abstract":"<p><p>Extracellular vesicles facilitate cell-to-cell communication, and some enveloped viruses utilize these vesicles as carriers to mediate viral transmission. SARS-CoV-2 envelope protein (2-E) forms a cation channel and overexpression of 2-E led to the generation of a distinct type of large extracellular vesicles (2-E-EVs). Although 2-E-EVs have been demonstrated to facilitate viral transmission in a receptor-independent way, the characteristics and biogenesis mechanism remain enigmatic. Via lipidomics and proteomic analysis, we found 2-E-EVs are distinct from endosome-derived exosomes. 2-E-EVs are notably enriched in Golgi apparatus components, aligning with the observed fragmentation in Golgi morphology. Through live cell imaging, we established a connection between 2-E-EVs formation, Golgi fragmentation, and channel activity, emphasizing the role of 2-E-EVs as ion channel-induced extracellular vesicles. Our work highlights 2-E-EVs as distinctive Golgi-derived vesicles, contributing to a deeper understanding of 2-E channel-mediated virus-host dynamics, with implications for therapeutic strategies and drug delivery.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695206","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}

{"title":"Isolation, identification, and challenges of extracellular vesicles: emerging players in clinical applications.","authors":"Xiaoxiao Ma, Lanwei Peng, Xiaohui Zhu, Tianqi Chu, Changcheng Yang, Bohao Zhou, Xiangwei Sun, Tianya Gao, Mengqi Zhang, Ping Chen, Haiyan Chen","doi":"10.1007/s10495-024-02036-2","DOIUrl":"https://doi.org/10.1007/s10495-024-02036-2","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) serve as critical mediators of intercellular communication, encompassing exosomes, microvesicles, and apoptotic vesicles that play significant roles in diverse physiological and pathological contexts. Numerous studies have demonstrated that EVs derived from mesenchymal stem cells (MSC-EVs) play a pivotal role in facilitating tissue and organ repair, alleviating inflammation and apoptosis, enhancing the proliferation of endogenous stem cells within tissues and organs, and modulating immune function-these functions have been extensively utilized in clinical applications. The precise classification, isolation, and identification of MSC-EVs are essential for their clinical applications. This article provides a comprehensive overview of the biological properties of EVs, emphasizing both their advantages and limitations in isolation and identification methodologies. Additionally, we summarize the protein markers associated with MSC-EVs, emphasizing their significance in the treatment of various diseases. Finally, this article addresses the current challenges and dilemmas in developing clinical applications for MSC-EVs, aiming to offer valuable insights for future research.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613632","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}

{"title":"Lenvatinib inhibits cholangiocarcinoma progression by targeting the FGF19/PI3K/AKT signaling pathway.","authors":"Yingcheng Wei, Lei Yang, Chenwei Tang, Hongkai Zhuang, Xinming Chen, Xiaowu Ma, Xuesong Deng, Yajin Chen, Wenliang Tan, Changzhen Shang","doi":"10.1007/s10495-024-02028-2","DOIUrl":"https://doi.org/10.1007/s10495-024-02028-2","url":null,"abstract":"<p><p>Cholangiocarcinoma (CCA) is known for its high aggressiveness and dismal prognosis, whose effectiveness of systemic therapy remains limited. As a multi-target drug, lenvatinib has exhibited promising effects in many solid tumors. However, the therapeutic role of lenvatinib in CCA is rarely investigated. Here, the in vitro assays including EdU, colony formation, transwell, wound healing, and apoptosis analyses demonstrated that lenvatinib significantly inhibited the proliferation, migration, and invasion, while simultaneously inducing apoptosis of CCA cells. Mechanistically, lenvatinib downregulated the expression of FGF19 and inactivated the PI3K/AKT signaling pathway. Depletion of FGF19 enhanced the anti-tumor effects of lenvatinib, which was attributed to the inhibition of p-PI3K and p-AKT expression in CCA cells. In contrast, overexpression of FGF19 activated the PI3K/AKT signaling pathway, thereby impairing the inhibitory effects of lenvatinib against CCA. In addition, the AKT inhibitor, MK-2206, reinforced the lenvatinib-induced CCA inhibition. Notably, the in vivo experiment confirmed that the subcutaneous tumorigenicity of CCA cells in nude mice was weakened by lenvatinib. Lenvatinib markedly downregulated the expression of FGF19, p-AKT, Ki-67, vimentin, and VEGF in the xenograft tumor tissues. Collectively, these findings demonstrated that lenvatinib inhibits CCA progression by targeting the FGF19/PI3K/AKT signaling pathway. The present study provides novel experimental evidence for the potential clinical application of lenvatinib in CCA, which also highlights the promising role of targeting FGF19 in combined therapeutic approaches for CCA.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613633","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}

{"title":"FBXO2 as a switch guides a special fate of tumor clones evolving into a highly malignant transcriptional subtype in oral squamous cell carcinoma.","authors":"Jingyi Cheng, Ousheng Liu, Xin Bin, Zhangui Tang","doi":"10.1007/s10495-024-02033-5","DOIUrl":"https://doi.org/10.1007/s10495-024-02033-5","url":null,"abstract":"<p><p>Tumors comprise a heterogeneous collection of tumor cells with distinct genetic and phenotypic characteristics that differentially promote malignant progression. Therefore, it is essential to depict the heterogeneous landscape of clones for understanding the cancer biology and overcoming the resistance of cancer therapy. To determine the dynamic clonal feature of OSCC, we constructed the evolutionary trajectory of tumor cells based on single-cell RNA sequencing data. A special transcriptional states of clones with distinct highly malignant features was identified, and FBXO2 was determined as the key switch gene causing the transition of tumor cells into this special state. FBXO2 exhibited a significantly high expression in OSCC than normal samples, especially in those with high clinical stages. The knockdown or overexpression of FBXO2 in OSCC cells correspondingly inhibited or promoted the abilities of proliferation, G1-S phase transition, migration, invasion, EMT, and resisting apoptosis. Moreover, FBXO2 was indicated to be involved in an intricate network to regulate multiple processes, modifying the interactions between tumor cells and other cells and thus defining different functional subtypes of tumor cells to affect tumor progression. These results provide new insights into clonal fate and pave the way for more effective therapy of OSCC.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563825","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}

{"title":"Advancements in programmed cell death research in antitumor therapy: a comprehensive overview.","authors":"Shuxin Wei, Chuangye Han, Shutian Mo, Hailian Huang, Xiaoling Luo","doi":"10.1007/s10495-024-02038-0","DOIUrl":"https://doi.org/10.1007/s10495-024-02038-0","url":null,"abstract":"<p><p>Cell death is a normal physiological process within cells that involves multiple pathways, such as normal DNA damage, cell cycle arrest, and programmed cell death (PCD). Cell death has been a hot spot of research in tumor-related fields, especially programmed cell death, which is a key form of cell death and is classified into different types according to the mechanism of occurrence, such as apoptosis, autophagy, necroptosis, pyroptosis, ferroptosis, and disulfidptosis. Given the important role of PCD in maintaining tissue homeostasis and inhibiting tumorigenesis and development, more and more basic and clinical studies are devoted to revealing its potential application in anti-tumor strategies. The purpose of this review is to systematically review the regulatory mechanisms of PCD and to summarize the latest research progress of anti-tumor treatment strategies based on PCD.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563780","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}

{"title":"Dysregulation of R-loop homeostasis shapes the immunosuppressive microenvironment and induces malignant progression in melanoma.","authors":"Yan Ouyang, Yan Gu, Shuqin Li, Xianpeng Wei, Yang Liu, Zejun Wang, Fuzhou Tang, Shichao Zhang","doi":"10.1007/s10495-024-02039-z","DOIUrl":"https://doi.org/10.1007/s10495-024-02039-z","url":null,"abstract":"<p><p>Dysregulated R-loop homeostasis leads to DNA replication stress and genomic instability, a major driver of cancer. However, the role of R-loops in melanoma development remains unclear. We established an R-loop scoring model based on a single-cell RNA sequencing dataset and evaluated the association between the R-loop score with the melanoma immune microenvironment and treatment response. We explored the role of CENPA-mediated changes in R-loop distribution during melanoma progression by DNA/RNA immunoprecipitation and sequencing and a series of functional experiments. We found that malignant cells with high R-loop scores may be involved in melanoma progression by modulating immune evasion, metabolic reprogramming, and cancer-related pathways. A cell communication analysis revealed that high-score R-loops play an important role in altering cell-cell interactions and limiting the CD8 + cytotoxic T cell response and T cell accumulation. CENPA silencing induced changes in R-loop distribution, upregulated Hippo signaling activity, and inhibited tumor cell proliferation and migration. Moreover, the R-loop score can predict the prognosis and immunotherapy effect of melanoma patients. Our work reveals the potential molecular mechanism by which abnormal R-loops promote melanoma progression, which may help develop anticancer therapies based on R-loops or R-loop regulators.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563782","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}