Cell insight最新文献

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Cell insight Pub Date : 2025-10-01 DOI: 10.1016/S2772-8927(25)00052-5

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Host-virus molecular arms race: RNAi-mediated antiviral defense and viral suppressor of RNAi 宿主-病毒分子军备竞赛：RNAi介导的抗病毒防御和RNAi的病毒抑制因子

Cell insight Pub Date : 2025-08-27 DOI: 10.1016/j.cellin.2025.100276

Bowen Zhang , Xi Zhou , Yujie Ren

{"title":"Host-virus molecular arms race: RNAi-mediated antiviral defense and viral suppressor of RNAi","authors":"Bowen Zhang , Xi Zhou , Yujie Ren","doi":"10.1016/j.cellin.2025.100276","DOIUrl":"10.1016/j.cellin.2025.100276","url":null,"abstract":"<div><div>RNA interference (RNAi) is a highly conserved post-transcriptional gene silencing (PTGS) mechanism widely presented in eukaryotes. During viral infection, double-stranded RNA viral replicative intermediate (vRI-dsRNA) derived from the viral genome is recognized and processed by Dicer to generate small interfering RNA (siRNA). The viral siRNA (vsiRNA) is subsequently loaded into the RNA-induced silencing complex (RISC), which targets and degrades viral RNAs to achieve antiviral immune response. During long-term evolution, viruses have evolved to counteract RNAi by encoding viral suppressors of RNAi (VSRs) through various strategies, thereby evading the immune clearance. Here we review how VSRs function as immune evasion factors against antiviral RNAi, along with their evolutionary significance in shaping both viral adaptation and host-pathogen co-evolution. We also discuss recent advancements and unresolved controversies regarding RNAi-mediated antiviral immunity in mammals. Finally, we provide a comprehensive analysis of emerging therapeutic strategies and vaccine designs that leverage the RNAi-VSR interaction mechanisms, while addressing their potential prospects and challenges in clinical translation.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 5","pages":"Article 100276"},"PeriodicalIF":0.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Faithful inheritance: Parental histone recycling and epigenetic memory in fission yeast 忠实遗传：裂变酵母亲本组蛋白循环和表观遗传记忆

Cell insight Pub Date : 2025-08-08 DOI: 10.1016/j.cellin.2025.100275

Yimeng Fang , Takenori Toda , Songtao Jia

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Cell insight Pub Date : 2025-08-01 DOI: 10.1016/S2772-8927(25)00042-2

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PAK4 phosphorylates and stabilizes MYC to promote acute myeloid leukemia PAK4磷酸化并稳定MYC促进急性髓性白血病

Cell insight Pub Date : 2025-07-31 DOI: 10.1016/j.cellin.2025.100274

Ting Xie , Peipei Sun , Hao Huang , Qilong Li , Hudan Liu , Jue Jiang

{"title":"PAK4 phosphorylates and stabilizes MYC to promote acute myeloid leukemia","authors":"Ting Xie , Peipei Sun , Hao Huang , Qilong Li , Hudan Liu , Jue Jiang","doi":"10.1016/j.cellin.2025.100274","DOIUrl":"10.1016/j.cellin.2025.100274","url":null,"abstract":"<div><div>MYC dysregulation plays a crucial role in acute myeloid leukemia (AML), yet the mechanisms governing its stabilization remain incompletely understood. MYC protein turnover is tightly regulated by post-translational modifications (PTMs), especially phosphorylation-dependent ubiquitination. Our previous study identified phosphorylation at MYC Serine 67 (S67) is critical to sustain its oncogenic activity in T-cell acute lymphoblastic leukemia (T-ALL). Here, we demonstrate that MYC S67 phosphorylation is also present in AML and catalyzed by p21-activated kinase 4 (PAK4). PAK4 directly binds MYC via its MBII domain, phosphorylates S67 and disrupts FBXW7-dependent ubiquitination, thereby stabilizing MYC to sustain MYC-driven leukemogenic programs. PAK4 inhibition destabilizes MYC and suppresses AML proliferation; however, it fails to elicit robust apoptosis, primarily due to the compensatory upregulation of the anti-apoptotic factor MCL-1. Combining the PAK4 inhibitor KPT-9274 with the MCL-1 antagonist S63845 induces synergistic lethality in AML cells. These findings provide the mechanistic insight of MYC stabilization in AML and establish a PAK4 inhibition-based targeted strategy as a promising therapeutic approach for AML treatment.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 5","pages":"Article 100274"},"PeriodicalIF":0.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Beyond interferons: Non-canonical roles of MITA/STING 超越干扰素：MITA/STING的非规范作用

Cell insight Pub Date : 2025-07-24 DOI: 10.1016/j.cellin.2025.100266

Liting Zhang , Chuchu Zhang , Junjie Zhang

{"title":"Beyond interferons: Non-canonical roles of MITA/STING","authors":"Liting Zhang , Chuchu Zhang , Junjie Zhang","doi":"10.1016/j.cellin.2025.100266","DOIUrl":"10.1016/j.cellin.2025.100266","url":null,"abstract":"<div><div>Mediator of IRF3 activation (MITA)/Stimulator of Interferon Genes (STING) (also known as MPYS/ERIS) is a crucial adaptor protein for initiating antiviral innate immune responses to intracellular DNA and DNA viruses. MITA binds cGAMP, a second messenger synthesized by cGAS in response to intracellular DNA, culminating in the induction of type I interferons (IFNs), inflammatory cytokines, and interferon-stimulated genes (ISGs). While the canonical IFN-dependent MITA signaling has been extensively studied, recent research has unveiled a growing repertoire of IFN-independent functions of MITA in various physiological processes and pathological conditions. These non-canonical roles of MITA are increasingly recognized for their involvement in critical processes such as antiviral activity, senescence, autophagy, metabolism, lysosomal biogenesis, and the development of neurological disorders. In this review, we summarize the latest advances in understanding MITA's non-canonical functions and provide insights into key scientific questions that remain to be addressed. Deciphering how MITA is involved in these complex physiological and pathological processes will not only deepen our understanding of MITA signaling, but may also offer new therapeutic targets for treating related diseases.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 5","pages":"Article 100266"},"PeriodicalIF":0.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Microbiota-derived bile acid metabolic enzymes and their impacts on host health 微生物来源的胆汁酸代谢酶及其对宿主健康的影响

Cell insight Pub Date : 2025-07-12 DOI: 10.1016/j.cellin.2025.100265

Haohan Ma , Kai Wang , Changtao Jiang

{"title":"Microbiota-derived bile acid metabolic enzymes and their impacts on host health","authors":"Haohan Ma , Kai Wang , Changtao Jiang","doi":"10.1016/j.cellin.2025.100265","DOIUrl":"10.1016/j.cellin.2025.100265","url":null,"abstract":"<div><div>Bile acids are amphipathic sterol molecules regulated by both the host and gut microbiota, serving as classical mediators for deciphering host-microbiota interactions. Synthesized primarily in the liver and undergoing extensive structural modifications along the gastrointestinal tract, bile acids are dynamically shaped by diverse bile acid metabolic enzymes, especially from gut microbiota. Beyond their canonical detergent-like functions, bile acids act as receptor modulators, immune regulators, and microbiota sculptors, profoundly involved in regulating host metabolic processes, maintaining immune homeostasis, and contributing to metabolic disorders when dysregulated. The modifications of bile acids by microbial enzymes critically influence their functional diversity. However, despite the vast array of bile acid modifications observed, significant gaps remain in the systematic identification and characterization of microbial bile acid metabolic enzymes. This review underscores the urgency of exploring the biosynthetic pathways for the production of key bile acids and highlights its potential to advance precision therapeutic strategies targeting gut microbiota and their enzymatic machinery.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 5","pages":"Article 100265"},"PeriodicalIF":0.0,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144772227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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The NF-κB-SLC7A11 axis regulates ferroptosis sensitivity in inflammatory macrophages NF-κB-SLC7A11轴调节炎性巨噬细胞对铁下垂的敏感性

Cell insight Pub Date : 2025-06-11 DOI: 10.1016/j.cellin.2025.100257

Mengjie Yang , Xiaowei Chen , Xiran Hu , Hexiang Li , Hao Huang , Yingzhe Fang , Jue Jiang , Hudan Liu , Yuan Wang , Guoliang Qing

{"title":"The NF-κB-SLC7A11 axis regulates ferroptosis sensitivity in inflammatory macrophages","authors":"Mengjie Yang , Xiaowei Chen , Xiran Hu , Hexiang Li , Hao Huang , Yingzhe Fang , Jue Jiang , Hudan Liu , Yuan Wang , Guoliang Qing","doi":"10.1016/j.cellin.2025.100257","DOIUrl":"10.1016/j.cellin.2025.100257","url":null,"abstract":"<div><div>M1-polarized macrophages exhibit remarkable resistance to ferroptosis, a form of regulated cell death driven by excessive lipid peroxidation. Yet the underlying mechanisms remain to be defined. Through CRISPR-based functional screen of metabolic genes combining transcriptomics analysis, we herein identified the cystine/glutamate antiporter SLC7A11 as a pivotal mediator of ferroptosis resistance in M1 macrophages. Mechanistically, lipopolysaccharide (LPS) engagement with the Toll-like receptor 4 (TLR4) resulted in NF-κB activation, leading to RELA-dependent transcriptional upregulation of <em>Slc7a11</em> expression. SLC7A11 in turn promoted cystine uptake and subsequent glutathione (GSH) synthesis. Genetic ablation of <em>Slc7a11</em> reduced GSH production, sensitizing M1 macrophages to RSL3-induced ferroptosis. In aggregate, our findings unveil the RELA-SLC7A11 axis as a critical metabolic checkpoint dictating macrophage ferroptosis sensitivity, which might be employed to modulate macrophage functions in inflammatory diseases.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 4","pages":"Article 100257"},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144517072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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TFAP4 exacerbates pathological cardiac fibrosis by modulating mechanotransduction TFAP4通过调节机械转导加剧病理性心脏纤维化

Cell insight Pub Date : 2025-06-02 DOI: 10.1016/j.cellin.2025.100256

Jie Liu , Jingjing Feng , Jingxuan Zhao , Xiangjie Kong , Zhangyi Yu , Yuanru Huang , Zechun He , Mengxin Liu , Zheng Liu , Zhibing Lu , Li Wang

{"title":"TFAP4 exacerbates pathological cardiac fibrosis by modulating mechanotransduction","authors":"Jie Liu , Jingjing Feng , Jingxuan Zhao , Xiangjie Kong , Zhangyi Yu , Yuanru Huang , Zechun He , Mengxin Liu , Zheng Liu , Zhibing Lu , Li Wang","doi":"10.1016/j.cellin.2025.100256","DOIUrl":"10.1016/j.cellin.2025.100256","url":null,"abstract":"<div><div>Cardiac fibroblast (CF) differentiation into myofibroblasts is a crucial driver of cardiac fibrosis, leading to extensive extracellular matrix (ECM) deposition that increases myocardial stiffness and eventually impairs heart function. Mechanotransduction has merged as a key regulator of CF activation and the fibrotic response post-myocardial infarction (MI). However, the molecular mechanisms linking CF activation to mechanical cues within the injured myocardium remain poorly understood. Here we identified transcription factor TFAP4 as a central regulator of fibrosis in both human and murine models. TFAP4 overexpression enhances CF proliferation, ECM protein expression, and myofibroblast differentiation. Notably, TFAP4 directly activates expression of mechanosensors including Itga11 and Piezo2, which are essential for transmitting mechanical signals that promote CF activation and fibrosis. Silencing <em>Itga11</em> and <em>Piezo2</em> reverses the pro-fibrotic effects of TFAP4, while TFAP4 downregulation in vivo reduces fibrosis and improves cardiac function post-MI. These findings identify TFAP4 as a pivotal link between mechanotransduction and fibrosis, suggesting it as a potential therapeutic target to mitigate fibrosis and enhance cardiac recovery following MI.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 4","pages":"Article 100256"},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Rapid and direct discovery of functional tumor specific neoantigens by high resolution mass spectrometry and novel algorithm prediction 通过高分辨率质谱和新的算法预测快速直接发现功能性肿瘤特异性新抗原

Cell insight Pub Date : 2025-06-01 DOI: 10.1016/j.cellin.2025.100251

Huajian Tian , Guifei Li , Cookson K.C. Chiu , E. Li , Yuzong Chen , Ting Zhu , Min Hu , Yanjie Wang , Suping Wen , Jiajia Li , Shuangxue Luo , Zhicheng Chen , Huimei Zeng , Nan Zheng , Jinyong Wang , Weijun Shen , Xi Kang

{"title":"Rapid and direct discovery of functional tumor specific neoantigens by high resolution mass spectrometry and novel algorithm prediction","authors":"Huajian Tian , Guifei Li , Cookson K.C. Chiu , E. Li , Yuzong Chen , Ting Zhu , Min Hu , Yanjie Wang , Suping Wen , Jiajia Li , Shuangxue Luo , Zhicheng Chen , Huimei Zeng , Nan Zheng , Jinyong Wang , Weijun Shen , Xi Kang","doi":"10.1016/j.cellin.2025.100251","DOIUrl":"10.1016/j.cellin.2025.100251","url":null,"abstract":"<div><div>While immune cell therapies have transformed cancer treatment, achieving comparable success in solid tumors remains a significant challenge compared to hematologic malignancies like non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). Over the past four decades, various immunotherapeutic strategies, including tumor vaccines, tumor-infiltrating lymphocyte (TIL) therapies, and T cell receptor (TCR) therapies, have demonstrated clinical efficacy in select solid tumors, suggesting potential advantages over CAR-T and CAR-NK cell therapies in specific contexts. The dynamic nature of the cancer-immunity cycle, characterized by the continuous evolution of tumor-specific neoantigens, enables tumors to evade immune surveillance. This highlights the urgent need for rapid and accurate identification of functional tumor neoantigens to inform the design of personalized tumor vaccines. These vaccines can be based on mRNA, dendritic cells (DCs), or synthetic peptides. In this study, we established a novel platform integrating immunoprecipitation-mass spectrometry (IP-MS) for efficient and direct identification of tumor-specific neoantigen peptides. By combining this approach with our proprietary AI-based prediction algorithm and high-throughput <em>in vitro</em> functional validation, we can generate patient-specific neoantigen candidates within six weeks, accelerating personalized tumor vaccine development.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 3","pages":"Article 100251"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0