Integrated Genomics Reveal Potential Resistance Mechanisms of PANoptosis‐Associated Genes in Acute Myeloid Leukemia

Molecular Carcinogenesis, Год журнала: 2025, Номер unknown

Опубликована: Янв. 27, 2025

Acute myeloid leukemia (AML) is marked by the proliferation of abnormal progenitor cells in bone marrow and blood, leading to low cure rates despite new drug approvals from 2017 2018. Current therapies often fail due emergence resistance mechanisms, such as those involving anti-apoptotic pathways immune evasion, highlighting an urgent need for novel approaches overcome these limitations. Programmed cell death (PCD) crucial tissue homeostasis, with PANoptosis-a form PCD integrating pyroptosis, apoptosis, necroptosis-recently identified. This process, regulated PANoptosome complex, could be key overcoming AML resistance. Targeting multiple simultaneously may prove more effective than single-target therapies. Research suggests that disrupting Bcl-2, can enhance sensitivity AML. study hypothesizes PANoptosis-associated genes (PARGs) play a critical role modulating responses offers multi-faceted approach tackle this challenge. Using RNA sequencing data Cancer Genome Atlas Gene Expression Omnibus databases, we performed differential expression analysis identify significantly dysregulated PARGs Regression identified prognostic PARGs, bridging gap understanding how contribute treatment We then verified their lines samples treated cytarabine using RT-qPCR. Hierarchical clustering revealed distinct PARG patterns, functional enrichment highlighted involvement immune-related pathways. The combination bioinformatics experimental validation underscores mediate modulation resistance, providing robust framework further study. Our findings suggest provide potential targets therapeutic intervention. highlights targeting improve outcomes By analyzing changes response standard clinical treatments, developing multi-target strategies disrupt programmed Such directly addresses limitations current treatments offering method mitigate potentially improving survival rates. underscore importance comprehensive mechanisms pave way innovative impact management.

Язык: Английский

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Glutathiones’ life in multi-cancers: especially their potential micropetides in liver hepatocellular carcinoma

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 18, 2025

Glutathione plays critical roles in detoxifying xenobiotics, cell signaling, death and the antioxidant defence an emerging body of evidence, most abundant intracellular low molecular weight thiol tissues. However, all glutathione metabolism pertinent genes (GMPGs) expression their diagnostic/prognostic/micropeptide potential analyses have not been investigated to perform pan-cancers. We gained GMPGs from MsigDB 7.2, 12,123 samples were used reveal differentially expressed (DEGs) survival analysis 32 types cancers TCGA, GTEx, GEO datasets for first time. All statistical performed by R bioinformatics, such as DEGs, prognostic, diagnostic analysis, ceRNA, micropeptide prediction immune infiltration. In addition, we utilized siRNA technology target knockdown G6PD gene Huh7 hepatocellular carcinoma cells. was significantly poor prognosis liver (LIHC) predicted RBM26-AS1 encoded might LIHC. vitro experiments show that knockout cells reduces proliferation, migration, invasion capabilities. confirmed played a crucial role occurrence progression is positively associated with Th2 LIHC, regulating responses system. considered be new player involved LIHC interacting G6PD, key function cancer.

Язык: Английский

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CDCA8 and its multifaceted role in tumorigenesis

Biomedicine & Pharmacotherapy, Год журнала: 2025, Номер 185, С. 117951 - 117951

Опубликована: Март 8, 2025

Язык: Английский

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Unravelling the Role of PANoptosis in Liver Diseases: Mechanisms and Therapeutic Implications

Liver International, Год журнала: 2025, Номер 45(4)

Опубликована: Март 21, 2025

PANoptosis is a multimodal form of cell death that involves inflammatory, apoptotic, and necroptotic pathways, playing key role in the development liver diseases. This article first outlines definition characteristics PANoptosis, then explores its mechanisms action different types diseases, including acute injury, failure, metabolic dysfunction-associated fatty disease, hepatocellular carcinoma. Furthermore, this analyses molecular regulatory network potential therapeutic targets. Finally, summarises current research on diseases future directions, it reviews emerging mechanism

Язык: Английский

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The molecular mechanisms, roles, and potential applications of PANoptosis in cancer treatment

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 29, 2025

PANoptosis, a newly identified form of programmed cell death regulated by the panoptosome complex, exhibits key characteristics apoptosis, pyroptosis and necroptosis. It exerts substantial influence on initiation progression spectrum diseases, particularly in cancer, where its impact is increasingly being recognized. PANoptosis closely related to tumorigenesis, carcinogenesis, metastasis, chemotherapy resistance, as well prediction therapeutic responses prognosis cancer patients. In this review, we first review discovery systematically analyze composition panoptosome. Subsequently, examine role various types encompassing function within tumor microenvironment, drug predictive prognosis. Ultimately, delve into strategies for targeting therapy, including molecules pathway, such ZBP1, RIPK1, RIPK3, Caspases other novel like nanoinducers viral vectors. This aims provide references assistance research application treatment.

Язык: Английский

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Nanomaterials‐Induced PANoptosis: A Promising Anti‐Tumor Strategy

Angewandte Chemie International Edition, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 19, 2024

Abstract Malignant tumors pose a significant threat to global public health. Promoting programmed cell death in cancer cells has become critical strategy for treatment. PANoptosis, newly discovered form of regulated death, integrates key molecular components pyroptosis, apoptosis, and necroptosis, activating these three pathways simultaneously achieve synergistic multi‐mechanistic killing. PANoptosis significantly inhibits growth resistance activates strong anti‐tumor immune response, making tumor‐specific induction potential therapeutic strategy. Currently, treatment research related is focused mainly on the development small molecules cytokines. However, approaches still face limitations terms metabolic stability tumor specificity. The unique physicochemical properties biological activities nanomaterials hold promise optimizing strategies. This review summarizes concept mechanisms highlights latest applications nanoagents PANoptosis‐based anti‐cancer therapy, discusses challenges future directions clinical translation. It hoped that this will inspire further exploration treatments, providing new perspectives researchers field.

Язык: Английский

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Bibliometric and visualized analysis on global trends and hotspots of TAK1 in regulated cell death: 1999 to 2024

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Окт. 15, 2024

Background Regulated cell death (RCD) is a genetically controlled form of that plays an important role in organogenesis, tissue remodeling, and pathogenesis cancers. Transforming growth factor-beta-activation kinase 1 (TAK1) member the serine/threonine protein family, which can respond to internal external stimuli participate inflammatory responses through multiple signaling pathways cellular processes. In last two decades, regulatory roles TAK1 at crossroads RCD pathways, including apoptosis, necroptosis, pyroptosis, PANoptosis were revealed by 801 articles retrieved from Web Science Core Collection database. To analyze global research trends hotspots concerning RCD, bibliometric visualized analysis applied current study. Methods The data for this bibliometrics study search formula was (TS=(Apoptosis) OR TS=(pyroptosis) TS=(Necroptosis) TS=(PANoptosis) TS=(Autophagy) TS=(Ferroptosis) TS=(cuproptosis)) AND ((TS=(TAK1)) TS=(MAP3K7)). co-occurrence co-cited on basic parameters conducted VOSviewer. dual-map overlay journals, citation bursts, keyword timelines, bursts analyzed CiteSpace. Results A total 46 countries have been included analysis. number publications demonstrates consistent increase 1999 2024. primary institutions driving field are Osaka University Notably, Journal Biological Chemistry stands out as most popular journal domain. These collectively involve contributions 4663 authors, with Jun Tsuji emerging prolific author. also gains highest co-citation frequency. Emerging encapsulated keywords, NF-κB, inflammation, autophagy, TNFα. Conclusion This first RCD. Based articles, results provide retrospective comprehensive view frontiers propose ideas guiding their future investigations molecular mechanisms therapeutic strategies field.

Язык: Английский

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Nanomaterials‐Induced PANoptosis: A Promising Anti‐Tumor Strategy

Angewandte Chemie, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 19, 2024

Abstract Malignant tumors pose a significant threat to global public health. Promoting programmed cell death in cancer cells has become critical strategy for treatment. PANoptosis, newly discovered form of regulated death, integrates key molecular components pyroptosis, apoptosis, and necroptosis, activating these three pathways simultaneously achieve synergistic multi‐mechanistic killing. PANoptosis significantly inhibits growth resistance activates strong anti‐tumor immune response, making tumor‐specific induction potential therapeutic strategy. Currently, treatment research related is focused mainly on the development small molecules cytokines. However, approaches still face limitations terms metabolic stability tumor specificity. The unique physicochemical properties biological activities nanomaterials hold promise optimizing strategies. This review summarizes concept mechanisms highlights latest applications nanoagents PANoptosis‐based anti‐cancer therapy, discusses challenges future directions clinical translation. It hoped that this will inspire further exploration treatments, providing new perspectives researchers field.

Язык: Английский

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Identification and validation of PANoptosis-based HNSCPAN-index as a prognostic model for head and neck squamous cell carcinoma

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Дек. 16, 2024

PANoptosis, a recently characterized form of programmed cell death, remains incompletely understood in the context Head and Neck Squamous Cell Carcinoma (HNSCC). In this study, we identified prognostically relevant set PANoptosis genes within The Cancer Genome Atlas (TCGA) database for HNSCC uncovered three molecular subtypes based on their expression profiles. Each subtype exhibited distinct prognostic outcomes immune infiltration patterns. To further elucidate clinical relevance, constructed risk score model, termed HNSCPAN-index, using least absolute shrinkage selection operator (LASSO) Cox regression differentially expressed across subtypes. Patients were stratified into high-risk low-risk groups according to HNSCPAN-index. predictive power model was evaluated Kaplan-Meier analysis, ROC, nomogram validated an external dataset. A lower HNSCPAN-index correlated with longer overall survival enhanced immunotherapy responses, whereas higher indicated increased sensitivity small-molecule targeted therapies. Moreover, demonstrated strong correlation chemotherapeutic drug sensitivity. Finally, DSCAM as key regulator HNSCC, where silencing death mediated by pyroptosis inducers. conclusion, revealed its potential role prognosis, TME, chemotherapy. These findings may provide deeper understanding pave way development more personalized therapeutic strategies.

Язык: Английский

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Mitochondrial Gene Scoring System: Predicting Prognosis and Precision Therapy for TACE Non-Response in Hepatocellular Carcinoma Patients

Journal of Cancer, Год журнала: 2024, Номер 16(2), С. 629 - 647

Опубликована: Дек. 31, 2024

Given the crucial role of mitochondria in prognosis and treatment hepatocellular carcinoma (HCC), we aim to develop two independent mitochondrial scoring systems separately predict patient likelihood transarterial chemoembolization non-response (TACE NR).

Язык: Английский

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