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Exosome-Mediated circRNA Hsa_Circ_0113050 Enhances Colorectal Cancer Cell Malignancy by Interacting with EIF4A3. 外泌体介导的circRNA Hsa_Circ_0113050通过与EIF4A3相互作用增强结直肠癌细胞恶性。
IF 2.6
DNA and cell biology Pub Date : 2025-09-01 Epub Date: 2025-07-14 DOI: 10.1177/10445498251359374
Yuan Tian, Chen He
{"title":"Exosome-Mediated circRNA Hsa_Circ_0113050 Enhances Colorectal Cancer Cell Malignancy by Interacting with EIF4A3.","authors":"Yuan Tian, Chen He","doi":"10.1177/10445498251359374","DOIUrl":"10.1177/10445498251359374","url":null,"abstract":"<p><p>The exosome-mediated circular RNAs (circRNAs) play a crucial role in tumorigenesis. The present study investigated the role of the exosome-mediated circRNA hsa_circ_0113050 in colorectal cancer (CRC) through its interaction with the eukaryotic translation initiation factor 4A3 (EIF4A3). CRC-derived exosomes were isolated and characterized by differential ultracentrifugation, transmission electron microscopy, and nanoparticle tracking analysis. The hsa_circ_0113050 expressions in CRC and exosomes were confirmed through a bioinformatic analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays. Cell functional and <i>in vivo</i> assays were applied to evaluate the effects of exosomes and hsa_circ_0113050 on CRC cell malignancy. The interaction between EIF4A3 and hsa_circ_0113050 was analyzed by RNA immunoprecipitation, Western blotting, and qRT-PCR assays. CRC-derived exosomes with diameters of 102 and 104 nm enhanced the ability of CRC cells to proliferate, migrate, and invade. hsa_circ_0113050 was highly expressed in CRC tissues and CRC-derived exosomes. Silencing hsa_circ_0113050 in exosomes effectively reversed the exosome-induced CRC cell malignancy. Furthermore, EIF4A3 bound to the linear gene (EIF3I) of hsa_circ_0113050 to enhance the hsa_circ_0113050 expression in the CRC cells. In conclusion, the present study is the first to reveal that exosome-mediated hsa_circ_0113050 enhances CRC cell malignancy by interacting with EIF4A3. Our study findings provide new mechanistic insights into circRNA regulation and highlight a potential therapeutic target for CRC.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":"512-521"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144628219","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
Bile Acid-Mediated Interactions with Various Cell Types in the Cholestatic Liver. 胆汁淤积肝中胆汁酸介导的各种细胞类型的相互作用。
IF 2.6
DNA and cell biology Pub Date : 2025-09-01 Epub Date: 2025-07-15 DOI: 10.1177/10445498251359370
Guanyi He, Jie Qing
{"title":"Bile Acid-Mediated Interactions with Various Cell Types in the Cholestatic Liver.","authors":"Guanyi He, Jie Qing","doi":"10.1177/10445498251359370","DOIUrl":"10.1177/10445498251359370","url":null,"abstract":"<p><p>Bile acids (BAs) have garnered significant attention due to their novel roles in modulating diverse host physiological processes. They play a crucial role in nutrient transport, organelle function, and maintaining the systemic balance of pro/anti-inflammatory states. BAs exert complex physiological effects through their interaction with nuclear receptors, such as farnesoid X receptor or cell membrane receptor Takeda G protein-coupled receptor 5. Disruption of BA transport and homeostasis results in the accumulation of BAs and elevated concentrations in the systemic circulation. This contributes to the pathogenesis of cholestatic disorders and is implicated in a variety of liver diseases, including primary biliary cholangitis and primary sclerosing cholangitis. In the context of cholestatic liver injury, BAs interact with parenchymal hepatocytes and nonparenchymal cells, leading to hepatocyte apoptosis, activation of hepatic stellate cells, and the initiation of inflammatory responses. Identifying key cellular and molecular components involved in this interaction may contribute to the development of potential therapies for cholestatic liver diseases. In this article, we provide a summary of the molecular mechanisms underlying BA-mediated interactions with various cell types in the cholestatic liver and discuss therapeutic strategies targeting BA pathways. We anticipate that a deeper understanding of these interactions will enable the formulation of novel strategies for the treatment of cholestatic liver injury.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":"502-511"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639018","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
Genetic Underpinnings of Mitochondrial Cardiomyopathy: A Scoping 2010-2024 Update. 线粒体心肌病的遗传基础:范围2010-2024更新。
IF 2.6
DNA and cell biology Pub Date : 2025-09-01 Epub Date: 2025-07-02 DOI: 10.1089/dna.2025.0089
Insaf Moudian, Joaira Bakkach, Zeineb Zian, Naima Ghailani Nourouti, Amina Barakat, Mohcine Bennani Mechita
{"title":"Genetic Underpinnings of Mitochondrial Cardiomyopathy: A Scoping 2010-2024 Update.","authors":"Insaf Moudian, Joaira Bakkach, Zeineb Zian, Naima Ghailani Nourouti, Amina Barakat, Mohcine Bennani Mechita","doi":"10.1089/dna.2025.0089","DOIUrl":"10.1089/dna.2025.0089","url":null,"abstract":"<p><p>Mitochondrial cardiomyopathy is a rare specific myocardial condition characterized by abnormal myocardium structure and/or function due to mitochondrial respiratory chain deficiency. This cardiac disorder results from mutations in mitochondrial DNA or nuclear genes affecting mitochondrial function. These mutations disrupt oxidative phosphorylation and consequently lead to energy deficit in the myocardial tissue and systemic symptoms due to impaired mitochondrial metabolism. In the current review, we aimed to highlight genetic and molecular underpinnings of mitochondrial cardiomyopathy. The impact of mitochondrial DNA characteristics on mitochondrial cardiomyopathy, mutations in both mitochondrial and nuclear genomes, as well as diagnostic limitations and future therapies, will be presented in this work.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":"473-485"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546632","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
Decoding Noncoding RNAs: Mastering Bone Morphogenetic Protein Signaling and Crosstalk Pathways for Breakthroughs in Periodontal Regeneration. 解码非编码rna:掌握骨形态发生蛋白信号和串扰通路在牙周再生中的突破。
IF 2.6
DNA and cell biology Pub Date : 2025-09-01 Epub Date: 2025-08-11 DOI: 10.1177/10445498251362766
Hamed Ghanati, Salar Motamedi, Shila Fallahpour, Ashkan Bayat, Moein Maddahi, Parisa Kazemi, Arezoo Aghakouchakzadeh, Arash Rezaee, Saba Hakimy, Mohammad Pirouzan, Mitra Rostami, Zahra Ebrahimvand Dibazar
{"title":"Decoding Noncoding RNAs: Mastering Bone Morphogenetic Protein Signaling and Crosstalk Pathways for Breakthroughs in Periodontal Regeneration.","authors":"Hamed Ghanati, Salar Motamedi, Shila Fallahpour, Ashkan Bayat, Moein Maddahi, Parisa Kazemi, Arezoo Aghakouchakzadeh, Arash Rezaee, Saba Hakimy, Mohammad Pirouzan, Mitra Rostami, Zahra Ebrahimvand Dibazar","doi":"10.1177/10445498251362766","DOIUrl":"10.1177/10445498251362766","url":null,"abstract":"<p><p>Regenerating periodontal tissues remains a significant hurdle in regenerative dentistry, requiring meticulous coordination of cellular and molecular mechanisms. Noncoding RNAs (ncRNAs), including microRNAs, long ncRNAs, and circular RNAs, are emerging as essential modulators of bone morphogenetic protein (BMP) signaling pathways, which are vital for processes such as osteogenesis, cementum formation, and periodontal ligament (PDL) repair. This review delves into the pivotal role of ncRNAs in influencing BMP signaling while briefly addressing their interaction with other critical pathways, such as transforming growth factor-beta, Activin, Wnt, Notch, mitogen-activated protein kinase, and PI3K. These ncRNAs act as dynamic regulators, fine-tuning BMP signaling to facilitate tissue differentiation, modulate inflammatory responses, and enhance extracellular matrix remodeling-key elements for addressing the complexity of periodontal tissue regeneration. By compiling the latest advancements, this review sheds light on the potential of ncRNAs as therapeutic targets, emphasizing their ability to refine BMP signaling for greater precision in tissue engineering. Moreover, the integration of ncRNA insights with advanced biomaterials and engineering solutions offers a promising direction for reconstructing the intricate bone-PDL-cementum complex. Framing ncRNAs as a central innovation in regenerative therapy, this review underscores their transformative potential in addressing the multifactorial challenges of periodontal repair and restoration.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":"486-501"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144823454","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
Effect of Licorice (Glycyrrhiza glabra)-Silver Nanoparticles on Liver and Kidney Histopathological Features in Common Carp Fish (Cyprinus carpio). 甘草-银纳米颗粒对鲤鱼肝脏和肾脏组织病理学特征的影响。
IF 2.6
DNA and cell biology Pub Date : 2025-09-01 Epub Date: 2025-07-14 DOI: 10.1089/dna.2025.0021
Hawre K Faraj, Nasreen M Abdulrahman
{"title":"Effect of Licorice (<i>Glycyrrhiza glabra</i>)-Silver Nanoparticles on Liver and Kidney Histopathological Features in Common Carp Fish (<i>Cyprinus carpio</i>).","authors":"Hawre K Faraj, Nasreen M Abdulrahman","doi":"10.1089/dna.2025.0021","DOIUrl":"10.1089/dna.2025.0021","url":null,"abstract":"<p><p>The increasing use of silver nanoparticles (AgNPs) in aquaculture has raised concerns regarding their potential toxic effects on fish health, particularly on vital organs, such as the liver and kidneys. Licorice (<i>Glycyrrhiza glabra</i>) root, known for its medicinal and antioxidant properties, has gained attention as a natural agent capable of mitigating such toxicity. Furthermore, licorice extract can be used in the eco-friendly green synthesis of AgNPs, acting as both a reducing and stabilizing agent, as confirmed by characterization techniques including X-ray diffraction, Fourier-transform infrared spectroscopy, and transmission electron microscopy. This study aimed to evaluate the protective effects of dietary licorice root powder against AgNP-induced histopathological and physiological damage in common carp (<i>Cyprinus carpio</i>). A total of 150 fish were randomly assigned to seven dietary treatment groups for 56 days, including a control group, three groups receiving increasing doses of AgNPs (2.5, 5, and 7.5 mg/kg feed), and three groups receiving corresponding combinations of same amount of AgNPs with licorice root powder (2.5, 5, and 7.5 g/kg feed). Histopathological evaluation revealed that AgNPs alone induced severe liver and kidney damage, including hydropic degeneration, necrosis, and inflammatory infiltration. In contrast, fish receiving licorice-supplemented diets showed significantly reduced tissue lesions, indicating hepatoprotective and nephroprotective effects. In conclusion, licorice root powder effectively mitigated AgNP-induced toxicity and improved organ health in common carp. The combination of licorice and AgNPs offers a promising alternative to antibiotics in aquaculture, enhancing sustainability and fish welfare. Further studies are recommended to investigate the underlying molecular mechanisms and optimize application strategies in fish diets and to investigate another model of animal.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":"522-532"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144628218","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
Mutations in Osteoclast Genes as Causes of Osteoclast-Related Diseases. 破骨细胞基因突变是导致破骨细胞相关疾病的原因。
IF 2.6
DNA and cell biology Pub Date : 2025-08-25 DOI: 10.1177/10445498251368298
Jelena M Živković, Jelena G Najdanović, Stevo J Najman
{"title":"Mutations in Osteoclast Genes as Causes of Osteoclast-Related Diseases.","authors":"Jelena M Živković, Jelena G Najdanović, Stevo J Najman","doi":"10.1177/10445498251368298","DOIUrl":"https://doi.org/10.1177/10445498251368298","url":null,"abstract":"<p><p>Osteoclasts, as the only cells capable of resorbing bone, play a significant role in all processes that take place at the level of bone tissue and are involved in the development of the skeleton, maintenance of its integrity, repair, and regeneration of bones. Therefore, it is not surprising that even small deviations from their normal functioning result in diseases that not only affect skeletal system but also the entire organism. There are a number of rare genetic bone diseases associated with mutations in osteoclast genes that govern their differentiation and function. Specifically, they are known as osteoclast-related diseases, and their main hallmark is either decreased or increased bone resorption. To understand the impact of osteoclast gene mutations on the course of these diseases, it is also necessary to know the cellular and molecular mechanisms underlying osteoclast development and function. Moreover, identification of specific gene mutations as potential therapeutic targets would be an important step in creating personalized gene therapies in the future.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983903","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
Molecular and Histopathology Diagnosis of Human Tegumentary Leishmaniasis Using Glycol Methacrylate-Embedded Samples: A New Approach for Referral Centers. 使用甲基丙烯酸乙二醇包埋样品的人类被膜利什曼病的分子和组织病理学诊断:转诊中心的一种新方法。
IF 2.6
DNA and cell biology Pub Date : 2025-08-20 DOI: 10.1177/10445498251361295
Cintia Xavier de Mello, Abraão Dornellas, Tatiana Queiroz, Rosimar Baptista de Lima, Lohaine Mafra, Caio Thomaz de Lima E Silva, Adriane Corrêa Gomes Duarte, Claude Pirmez, Marcia Pereira de Oliveira
{"title":"Molecular and Histopathology Diagnosis of Human Tegumentary Leishmaniasis Using Glycol Methacrylate-Embedded Samples: A New Approach for Referral Centers.","authors":"Cintia Xavier de Mello, Abraão Dornellas, Tatiana Queiroz, Rosimar Baptista de Lima, Lohaine Mafra, Caio Thomaz de Lima E Silva, Adriane Corrêa Gomes Duarte, Claude Pirmez, Marcia Pereira de Oliveira","doi":"10.1177/10445498251361295","DOIUrl":"https://doi.org/10.1177/10445498251361295","url":null,"abstract":"<p><p>Tegumentary leishmaniasis (TL) is a neglected tropical disease that affects approximately one million new patients living in endemic areas with a lack of health service infrastructure. In many countries, including Brazil, public referral centers provide diagnostic support using high-sensitivity and high-specificity tests. In this context, PCR has been increasingly used for diagnosis and other downstream applications, employing different clinical specimens and types of storage. However, new protocols must be developed to enable the use of PCR in specific tissue processing methods, such as those involving glycol methacrylate (GMA). This study aimed to evaluate the applicability of GMA-embedded biopsies as clinical specimens for diagnosis of TL by PCR. Thirty-five 3-µm sections were incubated at 55°C for 12 h in Tris-EDTA-NaCl buffer containing NP-40 detergent and proteinase K for DNA extraction. Twenty-five patients with clinical suspicion of TL were included. PCR detected <i>Leishmania</i> the kinetoplast DNA (kDNA) in 19 out of 23 (82.6%) patients with cutaneous lesions. Additionally, 13 out of 15 (81.2%) patients with cutaneous lesions displaying a histopathological pattern compatible with TL were also kDNA PCR positive. Only two patients with mucosal lesions were evaluated, and both tested positive by PCR. Our results demonstrate that GMA-embedded samples are suitable for diagnosis of TL by <i>Leishmania</i> kDNA PCR, highlighting their potential for clinical applications.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983826","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
Extracellular Vesicle-Liposome Hybrid Nanoparticles Delivery of CRISPR/Cas9 Induces a Unique DNA Repair Pattern in the HGF Gene of Stem Cells from Apical Papilla. 细胞外囊泡-脂质体混合纳米颗粒递送CRISPR/Cas9诱导顶乳头干细胞HGF基因的独特DNA修复模式
IF 2.6
DNA and cell biology Pub Date : 2025-08-20 DOI: 10.1177/10445498251370554
Razieh Yazdani, Mohammad Hossein Nasr Esfahani, Shahin Eghbalsaied, Fereshteh Karamali
{"title":"Extracellular Vesicle-Liposome Hybrid Nanoparticles Delivery of CRISPR/Cas9 Induces a Unique DNA Repair Pattern in the HGF Gene of Stem Cells from Apical Papilla.","authors":"Razieh Yazdani, Mohammad Hossein Nasr Esfahani, Shahin Eghbalsaied, Fereshteh Karamali","doi":"10.1177/10445498251370554","DOIUrl":"https://doi.org/10.1177/10445498251370554","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) have been investigated due to their natural biocompatibility and targeting capabilities. The specific approach of combining EVs with liposomes to create hybrid nanoparticles (ELNPs) for the delivery of the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas9) system for deletion of the HGF gene in stem cells, but their effectiveness in encapsulating large nucleic acids is limited due to their small size. This study aimed to knock out the HGF gene by the CRISPR/Cas9 system by ELNPs, and it was expected that the efficiency of the CRISPR/Cas9 system transfer would increase compared to the usual methods of using lipofectamine in stem cells from apical papilla (SCAPs). In this study, gRNA suitable for the HGF gene is designed first, and after insertion into the CRISPR/Cas9 vector, it enters Lipofectamine 2000. In the next step, ELNPs are prepared after collecting EVs and hybridizing them with liposomes containing CRISPR/Cas9 vector. Then, these integrated nanoparticles were presented to SCAPs, and the removal of HGF gene expression was evaluated at the level of RNA and protein. This study showed that the CRISPR/Cas9 system can be efficiently transferred to SCAP cells using ELNPs. Genomic DNA sequencing analyses of SCAP cells showed a unique pattern of mutation, highly likely mediated through EVs. Quantitative PCR and protein staining further showed a decrease in HGF gene expression in the knockout cells. Moreover, cell proliferation analysis showed a decrease in cell proliferation in KO-HGF adipose cells compared to the nonedited counterpart. In summary, this study highlights the supportive role of EVs in facilitating cell transfection and promoting a dominant DNA repair pattern, likely through an RNA-mediated mechanism, rather than the random insertions and deletions typically induced during CRISPR editing of the HGF gene in SCAPs.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983899","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
Mapping Cophosphoregulation Networks Linked to Transcriptional Regulator Bromodomain-Containing Protein 4. 定位与转录调控因子含溴域蛋白4相关的磷调控网络。
IF 2.6
DNA and cell biology Pub Date : 2025-08-01 Epub Date: 2025-06-12 DOI: 10.1089/dna.2025.0088
Anjana C Lalu, Fathimathul Lubaba, Athira Perunelly Gopalakrishnan, Althaf Mahin, Suhail Subair, Prathik Basthikoppa Shivamurthy, Athira C Rajeev, Rajesh Raju
{"title":"Mapping Cophosphoregulation Networks Linked to Transcriptional Regulator Bromodomain-Containing Protein 4.","authors":"Anjana C Lalu, Fathimathul Lubaba, Athira Perunelly Gopalakrishnan, Althaf Mahin, Suhail Subair, Prathik Basthikoppa Shivamurthy, Athira C Rajeev, Rajesh Raju","doi":"10.1089/dna.2025.0088","DOIUrl":"10.1089/dna.2025.0088","url":null,"abstract":"<p><p>Bromodomain-containing protein 4 (BRD4) is a pivotal transcriptional regulator implicated in cancer, fibrosis, and inflammation, yet its phospho-regulatory network remains underexplored. This study leverages an extensive analysis of 1000 qualitative and 225 quantitative global phosphoproteome datasets to decode the BRD4 phosphorylation landscape. We identified S601 and S1117 as predominant phosphorylation sites, driving the majority of BRD4 phospho-signaling. Co-regulation analysis revealed 755 and 972 proteins positively cophosphorylated with S601 and S1117, respectively, including key interactors like TRIM28 (S473) and PRKAR2A (S78), which enhance transcriptional activity and cAMP signaling. Upstream kinases MAPK14 and GRK5 emerged as high-confidence regulators of S1117 and S601, respectively, with correlations in breast cancer highlighting disease relevance. In addition, 93 phosphosites in 71 transcription factors co-regulated with S1117 and 69 in 53 with S601 underscore the role of BRD4 in transcription control. These findings unveil a complex phospho-signaling network, offering novel therapeutic targets for BRD4-associated diseases and a foundation for future experimental validation.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":"445-462"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277127","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
In Vitro Reconstitution of SPO11-Mediated DNA Cleavage Sheds New Light on the Initiation of Meiotic Recombination. spo11介导的DNA切割的体外重建为减数分裂重组的启动提供了新的思路。
IF 2.6
DNA and cell biology Pub Date : 2025-08-01 Epub Date: 2025-05-19 DOI: 10.1089/dna.2025.0091
Cédric Oger, Corentin Claeys Bouuaert
{"title":"<i>In Vitro</i> Reconstitution of SPO11-Mediated DNA Cleavage Sheds New Light on the Initiation of Meiotic Recombination.","authors":"Cédric Oger, Corentin Claeys Bouuaert","doi":"10.1089/dna.2025.0091","DOIUrl":"10.1089/dna.2025.0091","url":null,"abstract":"<p><p>Three recent studies report the first biochemical reconstitution of DNA double-strand break (DSB) formation by SPO11, the topoisomerase-derived transesterase that initiates meiotic recombination in sexually reproducing organisms. A central conclusion of these studies is that SPO11 is sufficient to catalyze DSBs <i>in vitro</i>, but cleavage is limited by the poor propensity of SPO11 to dimerize, thereby providing an effective mechanism to prevent uncontrolled breaks. The studies yield new insights into the mechanism of DNA DSB formation and raise new questions regarding the functions of SPO11 partners, the impact of the DNA substrate, the coordination between cleavage events, and the reversibility of the reaction.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":"401-406"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096425","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
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