Frontiers in Cell and Developmental Biology最新文献

{"title":"Diversity of <i>Drosophila</i> egg patterning: The missing tools to explore embryonic axis formation.","authors":"Helen L Stott, Nir Yakoby","doi":"10.3389/fcell.2025.1569318","DOIUrl":"10.3389/fcell.2025.1569318","url":null,"abstract":"<p><p>Focusing on selected model organisms to establish scientific communities and resources has greatly advanced our understanding of biological processes, including embryogenesis, and facilitated the translation of these data into developing human remedies. However, by restricting our research to a small number of model organisms, we risk overlooking the underlying mechanisms controlling animal diversity and speciation. Changes in cell signaling, protein compatibility, and genetic tinkering are often neglected due to the lack of molecular tools in non-traditional model organisms. The era of high-throughput genome sequencing, computational gene prediction, and emerging genome editing and imaging tools, offers an opportunity to explore novel mechanisms of organismal development and homeostasis. As we develop new model platforms, it is imperative to prioritize resources effectively. What criteria make an organism a \"good\" candidate for becoming a new model organism for exploring embryogenesis? The axis of the <i>Drosophila</i> embryo is set during eggshell patterning. Although species with a dorsal ridge exhibit dramatically different patterns of the dorsalization signal, epidermal growth factor receptor activation, compared to <i>Drosophila melanogaster</i>, the embryonic dorsal-ventral axis remains consistent. Despite the increasing number of sequenced fly species' genomes, the experimental tools necessary to study these species are still lagging. Here, we emphasize the need to further develop genetic and molecular tools for studying nontraditional model organisms to understand complex processes like evolution of maternal contribution and correct embryonic body axis. We address current challenges in achieving these goals, such as genetic markers, selectable markers, and the efficiency of CRISPR/Cas9 mediated genomic editing.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1569318"},"PeriodicalIF":4.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794579","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":"Translationally controlled tumor protein interacts with connexin 43 and facilitates intercellular coupling between cardiomyocytes.","authors":"Yaopeng Hu, Wenqian Cai, Yuko Hidaka, Keizo Hiraishi, Jiehui Cang, Masanari Umemura, Utako Yokoyama, Björn C Knollmann, Yoshihiro Ishikawa, Takayuki Fujita","doi":"10.3389/fcell.2025.1549063","DOIUrl":"10.3389/fcell.2025.1549063","url":null,"abstract":"<p><strong>Introduction: </strong>Connexins are gap junction proteins that play pivotal roles in intercellular communication. Connexin 43 (Cx43) is one of the most ubiquitously expressed connexin isoforms in human. Cx43 has been demonstrated to be involved in the pathological process of various diseases, including arrhythmias. Recently, translationally controlled tumor protein (TCTP), a highly conserved anti-apoptotic protein, has been shown to play an important role in protecting against the development of heart failure. However, its role in arrhythmogenesis remains unclear. In this study, we aimed to examine the interaction between TCTP and Cx43 and investigate the roles of TCTP in the formation of Cx43 gap junction channels and gap junctional intercellular communication (GJIC) in cardiomyocytes.</p><p><strong>Methods and results: </strong>We found that TCTP was predominantly expressed in the intercalated discs of mouse heart tissue. Cx43 in adult mouse hearts was coimmunoprecipitated using a TCTP-specific antibody. Additionally, co-localization of TCTP and Cx43 was demonstrated using a proximity ligation assay in iPS cell-derived human cardiomyocytes. TCTP silencing reduced the formation of Cx43 gap junction channels at the intercellular contacts between cardiomyocytes. Moreover, TCTP silencing significantly attenuated GJIC among cardiomyocytes. Interestingly, the development of ventricular arrhythmia was attenuated in cardiomyocyte-specific TCTP-overexpressing mice.</p><p><strong>Conclusion: </strong>These findings indicate that TCTP regulates GJIC. Thus, TCTP may be a therapeutic target for preventing Cx43-related pathogenesis.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1549063"},"PeriodicalIF":4.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779502","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":"Comprehensive analysis and validation of autophagy-related gene in rheumatoid arthritis.","authors":"Runrun Zhang, Wenhan Huang, Ting Zhao, Jintao Fang, Cen Chang, Dongyi He, Xinchang Wang","doi":"10.3389/fcell.2025.1563911","DOIUrl":"10.3389/fcell.2025.1563911","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is a chronic autoimmune disease in which autophagy is pivotal in its pathogenesis. This study aims to identify autophagy-related genes associated with RA and investigate their functional roles.</p><p><strong>Methods: </strong>We performed mRNA sequencing to identify differentially expressed genes (DEGs) between RA and osteoarthritis (OA) and intersected these with autophagy-related genes to obtain autophagy-related DEGs (ARDEGs) in RA. Bioinformatics and machine learning approaches were used to identify key biomarkers. Functional experiments, including real-time cellular analysis (RTCA), scratch healing, and flow cytometry, were conducted to examine the effects of gene silencing on the proliferation and migration of MH7A cells.</p><p><strong>Results: </strong>A total of 37 ARDEGs were identified in RA. Through bioinformatics analysis, interferon regulatory factor 4 (IRF4) emerged as a key hub gene, with its high expression confirmed in RA synovial tissues and RA FLS cells. IRF4 knockdown inhibited the proliferation and migration and promoted the death of MH7A cells.</p><p><strong>Conclusion: </strong>IRF4 is an autophagy-related diagnostic biomarker for RA. Targeting IRF4 could serve as a potential diagnostic and therapeutic strategy for RA, although further clinical studies are required to validate its effectiveness.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1563911"},"PeriodicalIF":4.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779466","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":"Cell protective effects of vitamin C against oxidative stress induced by ciprofloxacin on spermatogenesis: involvement of cellular apoptosis.","authors":"Nihal A Ibrahim, Manal A Buabeid, Kadreya E Elmorshedy, El-Shaimaa A Arafa","doi":"10.3389/fcell.2025.1489959","DOIUrl":"10.3389/fcell.2025.1489959","url":null,"abstract":"<p><strong>Introduction: </strong>Ciprofloxacin (CPFX), a second-generation fluoroquinolone, is widely used as an anti-infective agent for genitourinary tract infections due to its broad-spectrum efficacy against gram-positive and gram-negative organisms. Although CPFX is considered safe at therapeutic doses, recent evidence suggests its potential biological toxicity, particularly affecting testicular histology and function. This study aimed to investigate the effects of CPFX on testicular structure and function and to evaluate the protective role of vitamin C.</p><p><strong>Methods: </strong>Forty adult male albino rats were divided into four groups: control, CPFX-treated, vitamin C-treated, and CPFX combined with vitamin C-treated. After 60 days of treatment, blood samples were collected for hormonal assays, while testicular and epididymal tissues were analyzed using light and electron microscopy. Oxidative stress markers, including malondialdehyde (MDA), glutathione (GSH), and catalase (CAT) enzyme activity, were assessed. Statistical analyses were conducted using SPSS software.</p><p><strong>Results: </strong>Confocal microscopy of the CPFX-treated group revealed significant reductions in germ cell populations within seminiferous tubules, accompanied by severe apoptosis and degenerative epithelial changes. Morphometric analysis confirmed a decrease in tubular diameter and epithelial height, degeneration of spermatogenic cells, and detachment of apoptotic cells from the basement membrane. CPFX treatment significantly reduced testosterone levels and induced variable changes in gonadotropin hormones (LH and FSH). Co-administration of vitamin C with CPFX restored normal testicular morphology, preserving seminiferous tubule integrity and maintaining spermatogenic cell populations and spermatozoa within the lumen.</p><p><strong>Discussion and conclusion: </strong>Vitamin C supplementation effectively mitigated CPFX-induced oxidative stress by significantly reducing MDA levels and enhancing antioxidant defenses, including increased GSH content and CAT enzyme activity. These findings highlight the therapeutic potential of vitamin C in reversing CPFX-induced testicular toxicity by alleviating oxidative stress and restoring testicular function.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1489959"},"PeriodicalIF":4.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802818","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":"From genes to patterns: a framework for modeling the emergence of embryonic development from transcriptional regulation.","authors":"Jimena Garcia-Guillen, Ezzat El-Sherif","doi":"10.3389/fcell.2025.1522725","DOIUrl":"10.3389/fcell.2025.1522725","url":null,"abstract":"<p><p>Understanding embryonic patterning, the process by which groups of cells are partitioned into distinct identities defined by gene expression, is a central challenge in developmental biology. This complex phenomenon is driven by precise spatial and temporal regulation of gene expression across many cells, resulting in the emergence of highly organized tissue structures. While similar emergent behavior is well understood in other fields, such as statistical mechanics, the regulation of gene expression in development remains less clear, particularly regarding how molecular-level gene interactions lead to the large-scale patterns observed in embryos. In this study, we present a modeling framework that bridges the gap between molecular gene regulation and tissue-level embryonic patterning. Beginning with basic chemical reaction models of transcription at the single-gene level, we progress to model gene regulatory networks (GRNs) that mediate specific cellular functions. We then introduce phenomenological models of pattern formation, including the French Flag and Temporal Patterning/Speed Regulation models, and integrate them with molecular/GRN realizations. To facilitate understanding and application of our models, we accompany our mathematical framework with computer simulations, providing intuitive and simple code for each model. A key feature of our framework is the explicit articulation of underlying assumptions at each level of the model, from transcriptional regulation to tissue patterning. By making these assumptions clear, we provide a foundation for future experimental and theoretical work to critically examine and challenge them, thereby improving the accuracy and relevance of gene regulatory models in developmental biology. As a case study, we explore how different strategies for integrating enhancer activity affect the robustness and evolvability of GRNs that govern embryonic pattern formation. Our simulations suggest that a two-step regulation strategy, enhancer activation followed by competitive integration at the promoter, ensures more standardized integration of new enhancers into developmental GRNs, highlighting the adaptability of eukaryotic transcription. These findings shed new light on the transcriptional mechanisms underlying embryonic patterning, while the overall modeling framework serves as a foundation for future experimental and theoretical investigations.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1522725"},"PeriodicalIF":4.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779491","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":"Meiotic dynamics in a unique Australian marsupial provide new insights into the evolution of neo-sex chromosomes in the early stages of differentiation.","authors":"Laia Marín-Gual, Carolyn J Hogg, J King Chang, Andrew J Pask, Marilyn B Renfree, Paul D Waters, Aurora Ruiz-Herrera","doi":"10.3389/fcell.2025.1562403","DOIUrl":"10.3389/fcell.2025.1562403","url":null,"abstract":"<p><p>Understanding the origin and fate of sex chromosomes has been one of the most intriguing questions in biology. In therian (marsupial and eutherian) mammals, most species are characterized by a heteromorphic XX female XY male sex chromosome system. It is commonly accepted that they originated from a pair of autosomes after gaining a sex-determining function, leading to recombination suppression and subsequent Y chromosome degeneration. Unlike eutherian sex chromosomes which share a pseudo-autosomal region (PAR), the marsupial sex chromosomes are typically tiny and lack any homology. However, there is a lack of empirical evidence on biological systems that represent early stages of sex chromosome differentiation. Here, we describe the meiotic dynamics of an XY₁Y₂ system in the greater bilby (<i>Macrotis lagotis</i>: family Thylacomyidae) that resulted from a fusion between an autosome and the ancestral X chromosome. We compared the similarities and differences in the regulation of meiosis in two other Australian marsupial species with different sex chromosome systems: the tammar wallaby (<i>Macropus eugenii</i>: family Macropodidae) and the fat-tailed dunnart (<i>Sminthopsis crassicaudata</i>: family Dasyuridae), both with the ancestral XY system. We performed a cytological analysis of meiotic prophase I, including the study of chromosome synapsis, double strand break formation (as a proxy of recombination) and meiotic sex chromosome inactivation. Our results suggest that the neo-PAR in the greater bilby represents an early stage of differentiation, providing new insights into sex chromosome evolution.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1562403"},"PeriodicalIF":4.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779495","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":"CPP-calcification of articular cartilage is associated with elevated cytokine levels in synovial fluid.","authors":"Sina Stücker, Franziska Koßlowksi, Adrian Buchholz, Andrea Schwab, Agnieszka Halm-Pozniak, Christoph H Lohmann, Jessica Bertrand","doi":"10.3389/fcell.2025.1535530","DOIUrl":"10.3389/fcell.2025.1535530","url":null,"abstract":"<p><strong>Background: </strong>Calcification of articular tissues is commonly observed in later osteoarthritis (OA) stages and can be caused by basic calcium phosphate (BCP) or calcium pyrophosphate (CPP) crystals. Calcification, particularly CPP deposition, has recently been associated with inflammation and cellular senescence. Investigating this association, we analyzed the concentration of various inflammatory mediators in synovial fluid and synovial membrane of OA patients in relation to calcification and the different crystal types.</p><p><strong>Methods: </strong>Synovial fluid was collected from OA patients during joint replacement surgery. Cytokine concentrations were measured using magnetic bead-based multiplex assay using Luminex® technology. Radiographs were used to determine and grade calcification of the knee joint and involved calcium crystal types were identified via Raman spectroscopy.</p><p><strong>Results: </strong>Synovial fluid of patients with radiological calcification showed elevated levels of multiple cytokines (IL-10, IL-15, IL-1ra, GM-CSF), chemokines (IL-8, MCP-1, MIP-1b) and growth factors (PDGF-AB/BB, VEGF). Crystal differentiation revealed higher synovial fluid concentrations of IL-15, IL-1ra, IL-10, GM-CSF, PDGF-AB/BB and MIP-1b in patients with CPP- compared to BCP-calcified cartilage.</p><p><strong>Conclusion: </strong>We show an elevated cytokine profile in synovial fluid of patients with radiological calcification that may be linked to CPP depositison in cartilage.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1535530"},"PeriodicalIF":4.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771676","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":"Editorial: Lipids and membrane contacts - structure, functional aspects and implications on ageing, cell death and autophagy, volume II.","authors":"Christopher T Beh, Alexandre Toulmay, Patrick Rockenfeller","doi":"10.3389/fcell.2025.1589044","DOIUrl":"10.3389/fcell.2025.1589044","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1589044"},"PeriodicalIF":4.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771661","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":"Generation and characterization of induced pluripotent stem cells of small apes.","authors":"Yusuke Hamazaki, Hiroto Akuta, Hikaru Suzuki, Hideyuki Tanabe, Kenji Ichiyanagi, Takuya Imamura, Masanori Imamura","doi":"10.3389/fcell.2025.1536947","DOIUrl":"10.3389/fcell.2025.1536947","url":null,"abstract":"<p><p>Small apes (family Hylobatidae), encompassing gibbons and siamangs, occupy a pivotal evolutionary position within the hominoid lineage, bridging the gap between great apes and catarrhine monkeys. Although they possess distinctive genomic and phenotypic features-such as rapid chromosomal rearrangements and adaptations for brachiation-functional genomic studies on small apes have been hindered by the limited availability of biological samples and developmental models. Here, we address this gap by successfully reprogramming primary skin fibroblasts from three small ape species: lar gibbons (<i>Hylobates lar</i>), Abbott's gray gibbons (<i>Hylobates abbotti</i>), and siamangs (<i>Symphalangus syndactylus</i>). Using Sendai virus-based stealth RNA vectors, we generated 31 reprogrammed cell lines, five of which were developed into transgene-free induced pluripotent stem cells. These iPSCs displayed canonical features of primed pluripotency, both morphologically and molecularly, consistent with other primate iPSCs. Directed differentiation experiments confirmed the capacity of the small ape iPSCs to generate cells representing all three germ layers. In particular, their successful differentiation into limb bud mesoderm cells underscores their utility in investigating the molecular and developmental mechanisms unique to small ape forelimb evolution. Transcriptomic profiling of small ape iPSCs revealed significant upregulation of pluripotency-associated genes, alongside elevated expression of transposable elements. Remarkably, <i>LAVA</i> retrotransposons-a class of elements specific to small apes-exhibited particularly high expression levels in these cells. Comparative transcriptomic analyses with iPSCs from humans, great apes, and macaques identified evolutionary trends and clade-specific gene expression signatures. These signatures highlighted processes linked to genomic stability and cell death, providing insights into small ape-specific adaptations. This study positions small ape iPSCs as a transformative tool for advancing functional genomics and evolutionary developmental biology. By facilitating detailed investigations into hominoid genome evolution and phenotypic diversification, this system bridges critical gaps in comparative research, enabling deeper exploration of the genetic and cellular underpinnings of small ape-specific traits.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1536947"},"PeriodicalIF":4.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771744","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":"Arginase-II promotes melanoma and lung cancer cell growth by regulating Sirt3-mtROS axis.","authors":"Yang Yang, Andrea Brenna, Duilio M Potenza, Santhoshkumar Sundaramoorthy, Xin Cheng, Xiu-Fen Ming, Zhihong Yang","doi":"10.3389/fcell.2025.1528972","DOIUrl":"10.3389/fcell.2025.1528972","url":null,"abstract":"<p><strong>Background: </strong>Aberrant mitochondrial metabolism is a key source of massive mitochondrial reactive oxygen species (mtROS) in tumour cells. Arginase-II (Arg-II), a widely expressed mitochondrial metabolic enzyme, has recently been shown to enhance mtROS production and melanoma progression. However, how Arg-II enhances mtROS and whether mtROS is involved in stimulation of cancer cell proliferation and migration remain unclear.</p><p><strong>Methods and results: </strong>Here, we show that ablation of <i>arg-ii</i> suppresses cell growth, migration, nuclear deformation, and DNA damage in melanoma cells. Vice versa, overexpression of <i>arg-ii</i> in melanoma cells promotes melanoma cell growth and migration accompanied by enhanced nuclear deformation and DNA damage. Ablation or overexpression of <i>arg-ii</i> reduces or enhances mtROS, respectively, accounting for the effects of Arg-II on melanoma growth, migration, and DNA damage. Further data demonstrate that Arg-II enhances mtROS through decreasing Sirtuin 3 (Sirt3) levels. Silencing <i>sirt3</i> promotes melanoma growth, migration, nuclear deformation, and DNA damage through enhancing mtROS. In supporting of these findings, overexpression of <i>sirt3</i> prevented Arg-II-induced mtROS production with concomitant prevention of Arg-II-induced cell growth, migration, nuclear deformation and DNA damage. Furthermore, we show that upregulation of Arg-II under hypoxia induces nuclear deformation and DNA damage through suppressing Sirt3. Similar results are obtained in A549 human lung carcinoma cells. In addition, analysis of publicly accessible datasets reveals that elevated <i>arg-ii</i> mRNA levels in human tumor samples including skin cutaneous melanoma and lung cancers associate with poorer prognosis.</p><p><strong>Conclusion: </strong>Altogether, our findings demonstrate a critical role of Arg-II-Sirt3-mtROS cascade in promoting melanoma growth, migration, nuclear deformation, and DNA damage linking to melanoma progression and malignancy, which could be therapeutic targets for cancers such as melanoma and lung carcinoma.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1528972"},"PeriodicalIF":4.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771648","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}