Cell Death Discovery最新文献

{"title":"Hippo pathway and NLRP3-driven NETosis in macrophages: Mechanisms of viral pneumoniaaggravation.","authors":"Bijun Luo, Xiaoxia Wang, Jinyuan Lin, Jianlan Mo, Jia'an Xie, Yanqiong Zhou, Jifeng Feng, Linghui Pan","doi":"10.1038/s41420-025-02556-z","DOIUrl":"10.1038/s41420-025-02556-z","url":null,"abstract":"<p><p>Severe viral infections can precipitate acute lung injury, resulting in significant morbidity and mortality. While NETosis serves as an important defense mechanism against pathogens and viruses, its excessive or dysregulated activation may contribute to pulmonary damage. In this study, elevated levels of NETosis were detected in the peripheral blood of patients with viral pneumonia. To further investigate the relationship between NETosis and virus-induced acute lung injury, a murine model was established using intratracheal administration of poly(I:C), a synthetic analog of double-stranded RNA that mimics viral infection. NETosis biomarkers were assessed in both patients and poly(I:C)-stimulated mice. In addition, we examined the role of the Hippo signaling pathway and its downstream mediators, including inflammatory factors and chemokines. Enhanced NETosis and activation of the Hippo pathway were observed in the lungs of poly(I:C)-treated mice, along with elevated levels of IL-1β in isolated macrophages. These effects were mitigated by Hippo pathway inhibitors. Co-culture experiments confirmed that IL-1β promotes NETosis, while NLRP3, acting downstream of the Hippo pathway, was responsible for IL-1β secretion. Patients with viral pneumonia showed increased NLRP3 and IL-1β expression in monocyte-derived macrophages compared to healthy controls. Overall, our findings indicate that activation of the Hippo pathway in macrophages during poly(I:C) exposure upregulates NLRP3 and IL-1β expression, thereby promoting NETosis and exacerbating virus-induced lung injury. This study highlights a potential therapeutic target to reduce lung damage caused by viral infections.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"323"},"PeriodicalIF":6.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636312","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}

{"title":"CYP51A1 in health and disease: from sterol metabolism to regulated cell death.","authors":"Fangquan Chen, RuiRui Liang, Jieting Zhang, Rui Kang, Daolin Tang, Jiao Liu","doi":"10.1038/s41420-025-02621-7","DOIUrl":"10.1038/s41420-025-02621-7","url":null,"abstract":"<p><p>How do cells precisely coordinate sterol metabolism with survival and death signals in diverse physiological and pathological contexts? This fundamental question has gained increasing attention as accumulating evidence reveals that enzymes traditionally associated with lipid biosynthesis may have unexpected regulatory functions beyond metabolism. Cytochrome P450 family 51 subfamily A member 1 (CYP51A1), a conserved sterol 14α-demethylase essential for cholesterol synthesis, exemplifies this emerging concept. Although well-characterized as an antifungal drug target in microorganisms, the roles of human CYP51A1 in development, cell death regulation, and disease pathogenesis remain underexplored. Recent studies have uncovered that CYP51A1 not only contributes to cholesterol homeostasis but also modulates multiple forms of regulated cell death-including apoptosis, ferroptosis, alkaliptosis, and pyroptosis-via sterol intermediates or cholesterol-independent mechanisms. Moreover, dysregulation of CYP51A1 has been implicated in a wide spectrum of diseases, such as cancer, cataracts, Antley-Bixler syndrome, autoimmune disorders, metabolic liver disease and neurodegeneration. In this review, we provide a comprehensive synthesis of CYP51A1's structure, regulatory networks, and non-canonical functions. We propose a unifying framework in which CYP51A1 integrates metabolic reprogramming and cell fate control, highlighting its potential as a therapeutic target across diverse human diseases.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"322"},"PeriodicalIF":6.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636311","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}

{"title":"Metabolic reprogramming in colorectal cancer: a review of aerobic glycolysis and its therapeutic implications for targeted treatment strategies.","authors":"Boran Pang, Hao Wu","doi":"10.1038/s41420-025-02623-5","DOIUrl":"10.1038/s41420-025-02623-5","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains a significant oncological challenge, being among the foremost contributors to cancer-related mortality worldwide. This review summarizes our current knowledge regarding how metabolic reprogramming, specifically the Warburg effect, contributes to CRC pathobiology and explores its therapeutic relevance. Metabolic reprogramming in CRC is characterized by a shift from oxidative phosphorylation to glycolysis, termed the Warburg effect. Driven by the tumor microenvironment (TME), this adaptation enhances cancer cell proliferation through accelerated ATP generation, biosynthesis support, and redox balance. Key glycolytic enzymes, namely hexokinase, phosphofructokinase, pyruvate kinase, and lactate dehydrogenase are now prioritized as therapeutic targets in CRC treatment strategies. Diagnostic modalities utilizing CRC's altered metabolism such as 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) and metabolomic analysis of circulating metabolites, improved early detection through enhanced sensitivity and specificity. These approaches reveal CRC's distinct metabolic signatures, enabling precise disease stratification and management. Therapeutic strategies targeting the EMP pathway show preclinical efficacy in overcoming CRC-associated chemoresistance and radioresistance. Modulation of EMP-regulating pathways (AKT, AMPK, mTOR) provides additional therapeutic opportunities. However, CRC's metabolic heterogeneity demands multi-targeted approaches. The development of targeted therapies must consider the potential off-target effects on normal tissues that rely on EMP, necessitating a careful balance between therapeutic efficacy and safety. In summary, this review underscores the complexity of metabolic reprogramming in CRC and the need for a nuanced approach to target these pathways effectively. Subsequent investigations should prioritize defining tumor-selective metabolic vulnerabilities and engineering multi-pathway interventions that spare normal tissues, ultimately advancing therapeutic precision in CRC management.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"321"},"PeriodicalIF":6.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636313","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}

{"title":"Inhibition of VEGFR-3 by SAR131675 decreases renal inflammation and lymphangiogenesis in the murine lupus nephritis model.","authors":"Tian Wang, Wenjia Li, Ji-Hyun Yeom, Zhiheng Liu, Kyoung Min Kim, Kyung Pyo Kang","doi":"10.1038/s41420-025-02624-4","DOIUrl":"10.1038/s41420-025-02624-4","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune-complex deposits and inflammatory cell infiltrations in multiple organs. Approximately half of lupus patients have nephritis. Lymphangiogenesis is the proliferation of lymphatic vessels (LVs), which regulate tissue fluid homeostasis and immune cell trafficking, responding to the tissue environment. In this study, we evaluated the therapeutic effect of SAR131675, a selective VEGFR-3 inhibitor, on the murine lupus nephritis model by regulating inflammation and lymphangiogenesis. We evaluated biopsy-proven lupus nephritis with immunohistochemical staining for D2-40, a marker for human lymphatic endothelial cells. For animal experiments, 7- to 8-week-old male BALB/c mice were used. For the induction of a lupus-like model, the dorsal skin of mice was shaved and given topical treatment every other day with 100 μg resiquimod dissolved in 100 μL acetone during the 8-week treatment. We had renal histology and immunofluorescent study for inflammatory cells and lymphatic vessels. We also had a qRT-PCR and Western blot analysis to evaluate inflammatory cytokines and chemokines, lymphangiogenic factors, and TLR7/type I IFN response. A human study found that the higher the revised ISN/RPS LN histopathological classification and modified NIH activity indexes, the more D2-40 (+) lymphatic vessels were expressed in the tubulointerstitial areas. Inhibition of VEGFR-3 by oral SAR131675 treatment decreased the resiquimod-induced glomerular and tubulointerstitial inflammation and attenuated LYVE-1 (+) lymphatic vessel expression in the murine lupus model. Treatment SAR131675 decreased the resiquimod-induced increase of proinflammatory cytokines and chemokines by regulating TLR7/MyD88/IFN-α expression. This study suggests the therapeutic potential of targeting lymphatic proliferation by VEGFR-3 inhibition in lupus nephritis. Modulation of the lymphatic network may provide a novel approach to treating chronic inflammation and attenuating renal autoimmune response.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"320"},"PeriodicalIF":6.1,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616527","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}

{"title":"Rsk2 inhibition induces an aneuploid post-mitotic arrest of cell cycle progression in osteosarcoma cells.","authors":"Armelle Carreau, Christina Baldauf, Lena Warlich, Magdalena Weingartner, Laura Brylka, Michael Amling, Thorsten Schinke, Julia Luther","doi":"10.1038/s41420-025-02596-5","DOIUrl":"10.1038/s41420-025-02596-5","url":null,"abstract":"<p><p>Osteosarcoma is the most common primary bone tumor, which is associated with a high mortality rate. The c-Fos transgenic mouse model has been described to spontaneously develop osteosarcoma, and the ribosomal S6 kinase 2 (Rsk2) was found to be essential for c-Fos-induced osteosarcoma formation in mice. By isolating and characterizing osteosarcoma cell lines from FosTg and FosTg;Rsk2^-/y mice, we observed that Rsk2 deficiency impairs the growth advantage of FosTg cells. This can be explained by the aberrant number of nuclei due to impaired cytokinesis, inducing mitotic catastrophe. We therefore tested a pharmacological Rsk inhibitor (BI-D1870) for its ability to inhibit the proliferation of osteosarcoma cells and found that the effects observed by genetic Rsk2 inactivation were mimicked. BI-D1870 administration to FosTg cell lines led to reduced expression of Aurora kinase B. Therefore, the influence of a pharmacological Aurora kinase B inhibitor (Hesperadin) was tested. Similar to BI-D1870, Hesperadin caused impaired cytokinesis, resulting in the accumulation of polynuclear cells. This effect was also observed for two human osteosarcoma cell lines, U2OS and SaOS-2. Based on our findings, Rsk2 and/or Aurora kinase B can serve as potential targets for the design of new osteosarcoma therapies.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"318"},"PeriodicalIF":6.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12241552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599509","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}

{"title":"The transcriptomic fingerprint of cancer response to Tumor Treating Fields (TTFields).","authors":"Kerem Wainer-Katsir, Adi Haber, Hila Fishman, Lianghao Ding, Michael D Story, Renfei Du, Ulf D Kahlert, Laura Mannarino, Federica Mirimao, Monica Lupi, Maurizio D'Incalci, Gitit Lavy-Shahaf, Hila Ene, Roni Frechtel-Gerzi, Zeina Drawshy, Antonia Martinez-Conde, Eyal Dor-On, Yaara Porat, Moshe Giladi, Uri Weinberg, Yoram Palti","doi":"10.1038/s41420-025-02615-5","DOIUrl":"10.1038/s41420-025-02615-5","url":null,"abstract":"<p><p>Tumor Treating Fields (TTFields) therapy is an approved cancer treatment modality, based on non-invasive application of electric fields to the tumor region. Proteomic and cell biology methods revealed a versatile mechanism of action to be involved in the response to TTFields. In the current research we performed whole transcriptome analysis across tumor types to identify pan-cancer responses to TTFields. For this we collected samples from control and TTFields-treated human cancer cell lines of gastric cancer, pancreatic cancer, ovarian cancer, non-small cell lung carcinoma, pleural mesothelioma, and glioblastoma. The transcriptomic analysis supported previous reported effects: downregulation of pathways associated with cell cycle, cell growth, and proliferation; downregulation of DNA replication and the FA-BRCA DNA repair pathway; and upregulation of cellular responses to stress-senescence, autophagy, and apoptosis. Notably, previously unrecognized downstream effects of TTFields were revealed on cellular metabolism, with downregulation of protein and RNA metabolism, and upregulation of steroid biosynthesis. Additional DNA repair pathways were also found to be downregulated, including nucleotide excision repair, base excision repair, and mismatch repair. In conclusion, this study revealed similar response patterns to TTFields across different tumor types, re-enforcing some already pinpointed mechanisms, while revealing new mechanisms. Unlocking these new mechanisms may allow identification of potential new cancer treatments for application together with TTFields based on mechanistical compatibility.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"319"},"PeriodicalIF":6.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12246047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607522","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}

{"title":"ELAVL1-mediated USP29 mRNA degradation activates TAK1 driving M1 microglial polarization and neural stem cell differentiation dysregulation in spinal cord injury.","authors":"Chunhe Sha, Feng Pan, Xiaodong Liu, Zhiqing Wang, Guohui Liu, Kai Huang","doi":"10.1038/s41420-025-02604-8","DOIUrl":"10.1038/s41420-025-02604-8","url":null,"abstract":"<p><p>Spinal cord injury (SCI) represents a profound neurological condition characterized by motor dysfunction and sensory impairment. Microglial polarization significantly influences neurorepair and regeneration post SCI. This study aims to investigate the regulatory role of the ELAV-like RNA binding protein 1 (ELAVL1)-ubiquitin-specific peptidase 29 (USP29)-transforming growth factor beta-activated kinase 1 (TAK1) axis in microglial polarization and its effects on differentiation of neural stem cells (NSCs). A rat model of SCI was established via spinal cord transection at the tenth thoracic vertebra segment, followed by short hairpin RNA (shRNA) lentivirus infection. Motor function and coordination were evaluated while histopathological analysis of spinal cord tissues was conducted. Microglial polarization and NSC differentiation were assessed via immunofluorescence and Western blot analysis. In cellular experiments, lipopolysaccharide (LPS) was utilized to induce M1 polarization in HMC3 cells, with polarization status determined by flow cytometry, immunofluorescence, and WB. Co-immunoprecipitation, GST pull-down, and ubiquitination assays elucidated USP29 effects on TAK1 ubiquitination and activation. In SCI rat spinal cord tissues and LPS-treated HMC3 cells, we observed upregulation of ELAVL1 and phosphorylated level of TAK1, while USP29 expression was downregulated. ELAVL1 was found to bind USP29 mRNA, promoting its degradation and suppressing USP29 expression. USP29 directly interacted with TAK1, inhibiting its ubiquitination and phosphorylation. Knockdown of ELAVL1 significantly enhanced USP29 mRNA stability, inhibited TAK1 activation, promoted M2 microglial polarization, and suppressed M1 polarization. In vivo downregulation of ELAVL1 promoted the differentiation of NSCs into neurons by inhibiting M1 polarization and promoting M2 polarization, thereby improving motor function, alleviating nerve injury, and facilitating spinal cord repair. ELAVL1 exacerbates SCI pathology by degrading USP29 mRNA, thereby activating TAK1 and driving M1 microglial polarization. Targeting the ELAVL1-USP29-TAK1 axis may offer therapeutic potential for enhancing neurorepair in SCI. Schematic diagram of the ELAVL1-USP29-TAK1 axis mediating M1 microglial polarization and NSC differentiation dysregulation exacerbating SCI.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"317"},"PeriodicalIF":6.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12241534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599508","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}

{"title":"Circular RNA profiling identifies circ_0001522, circ_0001278, and circ_0001801 as predictors of unfavorable prognosis and drivers of triple-negative breast cancer hallmarks.","authors":"Dania Awata, Vishnubalaji Radhakrishnan, Hibah Shaath, Ramesh Elango, Sameera Rashid, Mohammed Akhtar, Thasni Karedath Abdul Azis, Ikhlak Ahmed, Khalid Ouararhni, Ammira S Al-Shabeeb Akil, Nehad M Alajez","doi":"10.1038/s41420-025-02576-9","DOIUrl":"10.1038/s41420-025-02576-9","url":null,"abstract":"<p><p>Breast cancer poses a significant clinical challenge due to its complex molecular landscape, underscoring the need for improved prognostic and therapeutic strategies. In this study, we explored the expression profiles and therapeutic relevance of circular RNAs (circRNAs) in a cohort of 96 breast cancer patients from Qatar representing the MENA region. Our data identified distinct expression patterns in relation to breast cancer subtypes, tumor grade, and age, with fifty circRNAs found to be associated with unfavorable relapse-free survival (RFS). The expression of sixteen of these circRNAs was validated in triple-negative breast cancer (TNBC) model using RNase R resistance assay. Among these, the expression of circ_0001522, circ_0001278, and circ_0001801 was validated using divergent primers, and their backsplice junctions were confirmed using Sanger sequencing. Functionally, siRNA-mediated knockdown of these circRNAs significantly suppressed cell proliferation, colony formation, three-dimensional organoid growth, and cell migration in TNBC models. Mechanistic investigations revealed that circRNA depletion altered a subset of miRNA and mRNA expressions, with key interactions involving miR-4458, miR-145-5p, and miR-760, regulating critical targets such as CCND1, ROBO4, and MMP1. Additionally, circRNA-RBP bioinformatic analysis identified common binding partners, including AGO2, CPSF7, TARDBP, UPF1, and LIN28B, suggesting roles in post-transcriptional regulation. Our data highlight circ_0001522, circ_0001278, and circ_0001801 as promising prognostic and therapeutic circRNA targets for breast cancer, offering new avenues for improving breast cancer prognosis and treatment.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"316"},"PeriodicalIF":6.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12241340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599482","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}

{"title":"The multifaceted roles of apolipoprotein E4 in Alzheimer's disease pathology and potential therapeutic strategies.","authors":"Yongfeng Chen, Haiping Jin, Jia Chen, Jing Li, Mihnea-Alexandru Găman, Zhenyou Zou","doi":"10.1038/s41420-025-02600-y","DOIUrl":"10.1038/s41420-025-02600-y","url":null,"abstract":"<p><p>Alzheimer's disease (AD), the most common dementia in the elderly, is marked by progressive cognitive decline and neurodegeneration. Core pathological hallmarks include amyloid-beta (Aβ) plaques, hyperphosphorylated tau aggregates, neuroinflammation, and metabolic dysfunction (e.g., impaired glucose utilization, mitochondrial deficits). Apolipoprotein E4 (ApoE4), the strongest genetic risk factor for AD, interacts with these processes, yet its precise pathogenic mechanisms remain unclear. This review examines ApoE4's multifaceted contributions to AD pathogenesis, focusing on its roles in Aβ accumulation, tau hyperphosphorylation, neuroinflammatory activation, and metabolic dysregulation. We further evaluate emerging therapeutic strategies targeting these pathways, including ApoE4 modulation, anti-amyloid/tau interventions, and metabolic rescue approaches. Elucidating the molecular interplay between ApoE4 and AD pathology is critical for developing targeted therapies to modify disease progression and mitigate cognitive decline in patients.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"312"},"PeriodicalIF":6.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590559","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}

{"title":"Role of non-coding RNA-regulated ferroptosis in colorectal cancer.","authors":"Yan-Peng Zhao, Jun-Liang Liu, Shuai Wang, Xue Li","doi":"10.1038/s41420-025-02606-6","DOIUrl":"10.1038/s41420-025-02606-6","url":null,"abstract":"<p><p>The recently discovered type of programmed cell death, termed ferroptosis, characterized by an iron-dependent accumulation of lipid peroxides, has been demonstrated to play a pivotal role in the progress of tumors. The role of non-coding RNAs (ncRNAs) in various malignant tumors has also been gradually elucidated in recent years. Colorectal cancer (CRC) is a malignant tumor with a high prevalence and mortality rate worldwide. Many recent studies have demonstrated that the effects of ncRNAs on CRC progression may be mediated by their regulation of ferroptosis. This review first outlines the fundamental mechanisms of ferroptosis and the role of ncRNAs in ferroptosis, and then we summarize the role of ferroptosis in CRC. We then focused on summarizing the effect of ncRNAs regulating ferroptosis in CRC and the recent progress of ferroptosis-related ncRNAs as prognostic biomarkers in CRC patients. This review will help to deepen our understanding of the ncRNA-ferroptosis-CRC axis and inform the study of potential therapeutic targets and prognostic markers for CRC patients.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"315"},"PeriodicalIF":6.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590557","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}