Cell reports最新文献

CDH3-AS1 antisense RNA enhances P-cadherin translation and acts as a tumor suppressor in melanoma. CDH3-AS1反义RNA增强P-cadherin翻译并在黑色素瘤中起抑瘤作用。

IF 6.9 1区生物学

Cell reports Pub Date : 2025-10-01 DOI: 10.1016/j.celrep.2025.116362

Manon Chadourne, Crystal Griffith, Neel Jasani, Xiaonan Xu, Emily Brennan, Olga Vera, Nicol Mecozzi, Kaizhen Wang, Alex M Jaeger, Florian A Karreth

{"title":"CDH3-AS1 antisense RNA enhances P-cadherin translation and acts as a tumor suppressor in melanoma.","authors":"Manon Chadourne, Crystal Griffith, Neel Jasani, Xiaonan Xu, Emily Brennan, Olga Vera, Nicol Mecozzi, Kaizhen Wang, Alex M Jaeger, Florian A Karreth","doi":"10.1016/j.celrep.2025.116362","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.116362","url":null,"abstract":"Thousands of regulatory non-coding RNAs (ncRNAs) have been annotated, yet their roles in gene regulation and cancer progression remain unclear. Mapping the landscape of ncRNA expression during melanoma progression revealed that ncRNAs represented nearly half of the deregulated genes, with antisense RNAs (asRNAs) comprising a large portion. CDH3-AS1, the most downregulated asRNA, overlaps the CDH3 gene, which encodes P-cadherin, a key cell adhesion protein that is reduced in melanoma. Overexpression of CDH3-AS1 increased cell aggregation and reduced xenograft tumor growth, mimicking the effects of CDH3. CDH3-AS1 interacted with CDH3 mRNA, increased ribosome occupancy, and enhanced P-cadherin translation through a mechanism resembling SINEB2 sequence to up-regulate translation (SINEUP)-mediated translational control. asRNAs complementary to 5' UTRs generally increase the ribosome occupancy of their cognate mRNAs, suggesting broader translational control through this mechanism. This study revealed CDH3-AS1-mediated enhancement of P-cadherin translation as a tumor-suppressive axis in melanoma and highlighted the broader potential of asRNAs as regulators of protein translation.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 10","pages":"116362"},"PeriodicalIF":6.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

USP9X is a mechanosensitive deubiquitinase that controls tumor cell invasiveness and drug response through YAP stabilization. USP9X是一种机械敏感性去泛素酶，通过YAP稳定控制肿瘤细胞侵袭性和药物反应。

IF 6.9 1区生物学

Cell reports Pub Date : 2025-10-01 DOI: 10.1016/j.celrep.2025.116372

Pierric Biber, Alexandrine Carminati, Walaa Mohager, Mickael Ohanna, Christophe A Girard, Margaux Lecacheur, Mira Kahil, Océane Bouvet, Marie Irondelle, Stéphane Audebert, Mehdi Khaled, Sophie Tartare-Deckert, Marcel Deckert

{"title":"USP9X is a mechanosensitive deubiquitinase that controls tumor cell invasiveness and drug response through YAP stabilization.","authors":"Pierric Biber, Alexandrine Carminati, Walaa Mohager, Mickael Ohanna, Christophe A Girard, Margaux Lecacheur, Mira Kahil, Océane Bouvet, Marie Irondelle, Stéphane Audebert, Mehdi Khaled, Sophie Tartare-Deckert, Marcel Deckert","doi":"10.1016/j.celrep.2025.116372","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.116372","url":null,"abstract":"Ubiquitin removal by deubiquitinases (DUBs) is crucial for protein activity and homeostasis. While tumor cells adapt to treatment and environmental stress, the role of DUBs in sensing mechanical signals from the extracellular matrix (ECM) remains an unexplored area. Using melanoma cells cultured on collagen matrices of varying stiffness and activity-based ubiquitin probe profiling combined with quantitative proteomics, we identify ubiquitin specific peptidase 9 X-linked (USP9X) as a stiffness-sensitive DUB acting through the discoidin domain receptor (DDR)/actomyosin signaling pathway. USP9X regulates levels of the mechanosensor YAP by preventing its proteasomal degradation via deubiquitination. Inhibition or knockdown of USP9X reduced YAP expression, impaired tumor cell migration, invasion, and ECM contraction, and decreased metastatic potential in vivo. Targeting USP9X also enhanced the effectiveness of BRAF-targeted therapies by limiting YAP-mediated mechanosensing, drug resistance, and tumor relapse. These findings establish USP9X as a mechanoresponsive DUB essential for cancer cell adaptation to mechanical cues, proposing it as a targetable mechanosensitive therapeutic target in cancer.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 10","pages":"116372"},"PeriodicalIF":6.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

SlWRKY14 integrates carotenoid and flavonoid biosynthetic pathways to regulate coloration and quality of tomato fruits. SlWRKY14整合了类胡萝卜素和类黄酮的生物合成途径，调节番茄果实的颜色和质量。

IF 6.9 1区生物学

Cell reports Pub Date : 2025-10-01 DOI: 10.1016/j.celrep.2025.116369

Yuanyuan Li, Fanliang Meng, Huiwan You, Zhiyong Shao, Chenyu Xu, Yuening Li, Songwen Li, Lihong Liu, Qiaomei Wang

{"title":"SlWRKY14 integrates carotenoid and flavonoid biosynthetic pathways to regulate coloration and quality of tomato fruits.","authors":"Yuanyuan Li, Fanliang Meng, Huiwan You, Zhiyong Shao, Chenyu Xu, Yuening Li, Songwen Li, Lihong Liu, Qiaomei Wang","doi":"10.1016/j.celrep.2025.116369","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.116369","url":null,"abstract":"Carotenoids and flavonoids are two principal classes of secondary metabolites in tomato fruit, jointly contributing to pigmentation and nutritional quality. Here, we identified SlWRKY14 as a novel regulator of both these two pathways. slwrky14 lines result in redder fruits enriched in carotenoids, whereas fruit-specific overexpression lines produce orange-yellow fruits with reduced carotenoids but elevated flavonoids. SlWRKY14 directly binds to the promoter of carotenoid biosynthetic genes (SlDXS1 and SlPSY1) and represses their transcription by recruiting histone deacetylase SlHDA1, which functions in decreased histone acetylation to inhibit gene expression. Further genetic evidence verifies the role of the SlWRKY14-SlHDA1 module in suppressing carotenoid accumulation. In contrast, SlWRKY14 activates the flavonoid biosynthetic gene SlPALA to promote flavonoid accumulation. Our findings demonstrate SlWRKY14 as a regulatory node of carotenoid and flavonoid biosynthesis, providing a strategy for coloration regulation and quality improvement without penalty of yield in tomato.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 10","pages":"116369"},"PeriodicalIF":6.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Break-induced replication is activated to repair R-loop-associated double-strand breaks in SETX-deficient cells. 在setx缺陷细胞中，断裂诱导复制被激活以修复r环相关的双链断裂。

IF 6.9 1区生物学

Cell reports Pub Date : 2025-09-30 DOI: 10.1016/j.celrep.2025.116386

Tong Wu, Youhang Li, Yuqin Zhao, Sameer Bikram Shah, Linda Z Shi, Xiaohua Wu

{"title":"Break-induced replication is activated to repair R-loop-associated double-strand breaks in SETX-deficient cells.","authors":"Tong Wu, Youhang Li, Yuqin Zhao, Sameer Bikram Shah, Linda Z Shi, Xiaohua Wu","doi":"10.1016/j.celrep.2025.116386","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.116386","url":null,"abstract":"The primary role of break-induced replication (BIR) is to repair single-ended double-strand breaks (seDSBs) generated at broken replication forks and eroding telomeres. In this study, we demonstrated that when senataxin (SETX), an RNA/DNA helicase, is defective, hyper-recombination using the BIR mechanism is induced at R-loops/hybrid-accumulated double-ended DSBs (deDSBs), uncovering a role for BIR in the repair of R-loops/hybrids-associated deDSBs. Intriguingly, the loss of SETX not only triggers non-canonical hyper-end resection requiring RAD52 and XPF but also stalls Polα-primase-initiated end-fill DNA synthesis due to the accumulation of RNA/DNA hybrids on single-strand DNA (ssDNA) overhangs at deDSBs. This conflict between fill-in DNA synthesis and accumulated hybrids induces PCNA ubiquitination and PIF1 loading, thereby initiating the BIR mechanism at deDSBs. Hyper-resection further enhances PCNA ubiquitination and PIF1 loading, driving BIR-mediated hyper-recombination. Moreover, dysfunctional SETX is synthetic lethal with loss of PIF1, RAD52, or XPF, offering new strategies for targeted treatment of SETX-deficient tumors.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 10","pages":"116386"},"PeriodicalIF":6.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Single-cell analysis uncovers preserved prostate cancer lineages and universally altered pathways in Matrigel-free patient-derived organoids. 单细胞分析揭示了保存的前列腺癌谱系和普遍改变的途径在无matrigel的患者来源的类器官。

IF 6.9 1区生物学

Cell reports Pub Date : 2025-09-30 DOI: 10.1016/j.celrep.2025.116352

Robin Dolgos, Romuald Parmentier, Jing Wang, Raphaëlle Servant, Arnoud J Templeton, Tobias Zellweger, Alastair D Lamb, Kirsten D Mertz, Svetozar Subotic, Tatjana Vlajnic, Helge Seifert, Ashkan Mortezavi, Cyrill A Rentsch, Lukas Bubendorf, Clémentine Le Magnen

{"title":"Single-cell analysis uncovers preserved prostate cancer lineages and universally altered pathways in Matrigel-free patient-derived organoids.","authors":"Robin Dolgos, Romuald Parmentier, Jing Wang, Raphaëlle Servant, Arnoud J Templeton, Tobias Zellweger, Alastair D Lamb, Kirsten D Mertz, Svetozar Subotic, Tatjana Vlajnic, Helge Seifert, Ashkan Mortezavi, Cyrill A Rentsch, Lukas Bubendorf, Clémentine Le Magnen","doi":"10.1016/j.celrep.2025.116352","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.116352","url":null,"abstract":"The application of patient-derived organoids (PDOs) in prostate cancer (PCa) research has been hampered by poor take rates and benign overgrowth. We highlight the limitations of existing culture conditions and identify extracellular matrix composition as a determinant of organoid outcome. Single-cell RNA sequencing reveals that Matrigel-free PDOs exhibit cellular heterogeneity, preserve patient-specific PCa cells with active androgen receptor signaling, and enrich in intermediate cells. In contrast, Matrigel fails to maintain primary PCa cells and produces in vitro basal-like features divergent from patient samples. Furthermore, we redefine cell-type signatures, identify biomarkers discriminating tumor versus other cell types, and show that expression of laminin-binding integrins is a hallmark of Matrigel-derived organoids. Finally, integrating previously published datasets with our data, we generate a prostate PDO single-cell atlas (PPScA), which captures a spectrum of cellular identities while revealing pathways altered in vitro. Our study provides methodological improvements for short-term culture and cellular biology insights.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 10","pages":"116352"},"PeriodicalIF":6.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Sensory origin of visually evoked activity in auditory cortex. 听觉皮层视觉诱发活动的感觉来源。

IF 6.9 1区生物学

Cell reports Pub Date : 2025-09-30 DOI: 10.1016/j.celrep.2025.116364

Timothy Olsen, Andrea Hasenstaub

引用次数: 0

A hexamer tandem repeat RNA embedded within an SVA retrotransposon drives R-loop formation and neurodegeneration. 嵌入SVA反转录转座子内的六聚体串联重复RNA驱动r环形成和神经变性。

IF 6.9 1区生物学

Cell reports Pub Date : 2025-09-30 DOI: 10.1016/j.celrep.2025.116393

Laura D'Ignazio, Alan P R Lorenzetti, Ellen B Penney, Taylor A Evans, Bareera Qamar, Alejandra E McCord, Arthur S Feltrin, Andre R Barbosa, Bonna J Sheehan, Bruno Araujo, Hunter H Giles, Yanhong Wang, Tomoyo Sawada, Michael Zabolocki, Micaela Murcar, Cara Fernandez-Cerado, G Paul Legarda, Michelle Sy, M Salvie Velasco-Andrada, Edwin Munoz, Mark C Ang, Cid Czarina E Diesta, Cedric Bardy, D Cristopher Bragg, Apua C M Paquola, Jennifer A Erwin

引用次数: 0

Phosphorylation-dependent suppression of SERRATE balances miRNA metabolism in planta. SERRATE磷酸化依赖性抑制平衡植物miRNA代谢。

IF 6.9 1区生物学

Cell reports Pub Date : 2025-09-30 DOI: 10.1016/j.celrep.2025.116367

Lingli Zheng, Hongwei Xue

引用次数: 0

Bile acid synthesis dysregulation in liver diseases promotes ectopic expansion of oral streptococci in the intestine. 肝脏疾病中的胆汁酸合成失调促进肠道内口腔链球菌的异位扩张。

IF 6.9 1区生物学

Cell reports Pub Date : 2025-09-30 DOI: 10.1016/j.celrep.2025.116374

Yugui Wang, Wenjie Mu, Jian Guan, Pingping Ma, Yaqi Li, Ying Zhang, Wenjun Zhu, Yu Zhou, Yang Zou, Tongxu Zeng, Jian Zhou, Xiaoqi Lin, Xuehua Yan, Wenjuan Shi, Xiaola Guo, Xing-Quan Zhu, Xuepeng Cai, Yan Sun, Aijiang Guo, Shuai Wang

{"title":"Bile acid synthesis dysregulation in liver diseases promotes ectopic expansion of oral streptococci in the intestine.","authors":"Yugui Wang, Wenjie Mu, Jian Guan, Pingping Ma, Yaqi Li, Ying Zhang, Wenjun Zhu, Yu Zhou, Yang Zou, Tongxu Zeng, Jian Zhou, Xiaoqi Lin, Xuehua Yan, Wenjuan Shi, Xiaola Guo, Xing-Quan Zhu, Xuepeng Cai, Yan Sun, Aijiang Guo, Shuai Wang","doi":"10.1016/j.celrep.2025.116374","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.116374","url":null,"abstract":"Liver diseases often coincide with dysregulated gut homeostasis and Streptococcus overgrowth, yet the underlying mechanisms remain unclear. Here, we study patients with liver echinococcosis and other liver conditions. We observe that these patients frequently exhibit a co-occurrence of an ectopic expansion of orally derived Streptococcus species implicated in intestinal inflammation, alongside a bile acid deficiency in the gut. This association is typically characterized by the reduction of 12-ketolithocholic acid (12-KetoLCA), which exerts potent membrane-disrupting activity. We show that liver disorders compromise gut resistance to oral microbes due to a loss of ecological control from bile acids, particularly 12-KetoLCA. This bile-acid-conferred gut barrier is regulated by cytochrome P450 enzymes and can be reconstituted through adeno-associated virus (AAV) gene therapy targeting these genes. Additionally, we reveal that supplementation with 12-KetoLCA prevents oral Streptococcus-driven gut inflammation through antibacterial activity. Our findings underscore the essential role of bile acids in maintaining the oral-gut barrier.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 10","pages":"116374"},"PeriodicalIF":6.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

A single-dose nanoparticle vaccine protects against mpox in preclinical models. 在临床前模型中，单剂量纳米颗粒疫苗可预防m痘。

IF 6.9 1区生物学

Cell reports Pub Date : 2025-09-30 DOI: 10.1016/j.celrep.2025.116358

Run-Yu Yuan, Meng-Jun Li, Xiao-Bing Lin, Xin Zhang, Fei Yu, Xiao Zhang, Qi Qian, Yun Peng, De-Lin Li, Qin-Jian Zhao, Hui Zhang, Yang Yang, Chen-Guang Shen, Bai-Sheng Li, Yin-Feng Kang

{"title":"A single-dose nanoparticle vaccine protects against mpox in preclinical models.","authors":"Run-Yu Yuan, Meng-Jun Li, Xiao-Bing Lin, Xin Zhang, Fei Yu, Xiao Zhang, Qi Qian, Yun Peng, De-Lin Li, Qin-Jian Zhao, Hui Zhang, Yang Yang, Chen-Guang Shen, Bai-Sheng Li, Yin-Feng Kang","doi":"10.1016/j.celrep.2025.116358","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.116358","url":null,"abstract":"The ongoing outbreak and emergence of monkeypox virus (MPXV) clade Ib and IIb lineage have heightened its transmissibility, morbidity, and mortality, underscoring the urgent need for safe and effective vaccines against MPXV infection. In this study, we developed a \"two-in-one\" nanoparticle vaccine, DAM-NP, which incorporates bivalently fused M1 and A35 antigens conjugated to a self-assembled 24-meric ferritin nanoparticle. Preclinical evaluations demonstrated that DAM-NP elicits robust humoral and cellular immune responses, providing complete protection against lethal vaccinia virus challenge. Importantly, pre-existing antibodies resulting from prior infection with the VACV Tiantan strain utilized for smallpox prevention did not diminish vaccine efficacy. A single dose was sufficient to prevent both morbidity and mortality following a lethal MPXV challenge. These findings establish DAM-NP as a highly immunogenic and promising single-dose vaccine candidate for prevention of MPXV and other orthopoxvirus infections.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 10","pages":"116358"},"PeriodicalIF":6.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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