Epigenetics最新文献

{"title":"Alterations in epigenetic marks and expression of genes related to stress regulation: an exploratory study among newborns after fetal repair of spina bifida aperta.","authors":"M A Landolt, N L Strebel, U Moehrlen, N Ochsenbein, N Strübing, T Burkhardt, C D'Addario, M Pucci, A Bodenmann, E Grünblatt","doi":"10.1080/15592294.2026.2632976","DOIUrl":"10.1080/15592294.2026.2632976","url":null,"abstract":"<p><p>Fetal repair of spina bifida aperta (fSBA) is an established intervention that improves neurological and neurodevelopmental outcomes. The present exploratory study examines whether molecular signatures related to stress regulation are detectable in newborns following this procedure. Specifically, we investigated DNA methylation and gene expression of two stress-regulatory genes, <i>NR3C1</i> and <i>FKBP5</i>. Within a clinical trial (ID: NCT04027374), we analyzed postpartum saliva samples from newborns who had undergone fSBA repair (fSBA group; <i>n</i> = 30) and compared them with two control groups: newborns exposed to antenatal glucocorticoids for lung maturation (LMI group; <i>n</i> = 12) and healthy controls (HC group; <i>n</i> = 27). Pyrosequencing and qRT-PCR were used for epigenetic and transcriptional analyses. Significant group differences were observed in <i>FKBP5</i> methylation, particularly at intron 7 CpG sites 5-7. The fSBA group showed lower methylation at site 5 but higher methylation at sites 6-7 compared to controls. No significant methylation differences were detected for <i>NR3C1</i>. Conversely, <i>NR3C1</i> gene expression was elevated in the fSBA group, whereas <i>FKBP5</i> expression did not differ between groups. These findings suggest gene- and site-specific molecular variation in newborns following fetal surgery. Given the exploratory nature of the study, the results are not suited to draw specific clinical implications but may inform future work aimed at understanding stress-related molecular alterations surrounding fetal interventions. Larger and longitudinal studies are warranted to clarify the robustness, developmental course, and potential clinical relevance of these molecular patterns.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"21 1","pages":"2632976"},"PeriodicalIF":3.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12973468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147376427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential DNA methylation clock ages across buffy coat (BC), peripheral blood mononuclear cells (PBMC), and saliva in individuals in early-to-mid adulthood.","authors":"Ryan Bruellman, Donald Evans, Andrew Smolen, Luke M Evans, Chandra A Reynolds","doi":"10.1080/15592294.2026.2653960","DOIUrl":"10.1080/15592294.2026.2653960","url":null,"abstract":"<p><p>Epigenetic aging prior to midlife is gaining interest as an intervenable period to address health and cognitive aging. Epigenetic changes may index DNA methylation aging rates, but methylation profiles may not be substitutable across tissues. We compared DNA methylation clocks and age acceleration in saliva, buffy coat (BC), and peripheral blood mononuclear cells (PBMC) collected in 91 individuals (7 unpaired, 20 siblings, 64 twins; 18 monozygotic (MZ), 14 dizygotic (DZ) pairs) from the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife1; Mean age = 30.90 years [range = 28.07-41.13]; 50.5% female). Across 15 DNA methylation clocks, chronological age and DNA methylation ages were moderately associated (mean Spearman correlations: <i>r</i> = 0.37, Saliva; <i>r</i> = 0.40, BC; <i>r</i> = 0.34, PBMC). In mixed-effects models, saliva showed higher DNA methylation ages (<i>B</i> = 3.77-19.72 years vs BC, <i>p</i> < 0.001), whereas PBMC and BC were comparable (<i>B</i> = -0.06-0.39 years vs BC, <i>p</i> ≥ 0.436). The exception was the next-generation clock DunedinPace showing comparability (<i>p</i> = 0.486). Similar patterns were observed for age acceleration estimates. Altogether, MZ pairs (meta-analytic <i>r =</i> 0.49, 95%CI = 0.32,0.66) and DZ pairs (meta-analytic <i>r =</i> 0.38, 95%CI = 0.25,0.52) were moderately correlated (Spearman), but MZ pairs showed heterogeneity across tissues (<i>p</i> < 0.034): saliva was lower (mean <i>r =</i> 0.33, <i>SD</i> = 0.25) than BC (mean <i>r =</i> 0.64, <i>SD</i> = 0.10) and PBMC (mean <i>r =</i> 0.49, <i>SD</i> = 0.18). Next-generation PCGrimAge and DunedinPace clocks showed consistent zygosity correlations across tissues, while multi-tissue clocks (e.g. ZhangQ) showed comparable MZ-DZ correlations. While saliva-based DNA methylation is not a direct substitute for blood-based DNA methylation, BC and PBMC show comparability; nevertheless, all tissue types may be appropriate for DNA methylation aging studies when compared within tissues.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"21 1","pages":"2653960"},"PeriodicalIF":3.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13085942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple generation distinct toxicant exposures and epigenetic transgenerational inheritance of sex‑specific outcross impacts on sperm epigenetics and obesity pathology.","authors":"Sarah De Santos, Eric E Nilsson, Alexandra A Korolenko, Michael K Skinner","doi":"10.1080/15592294.2026.2719246","DOIUrl":"10.1080/15592294.2026.2719246","url":null,"abstract":"<p><p>Environmental factors can influence the epigenetic inheritance of pathology across generations. Prior studies found various toxicants increased pathology in their descendants through epigenetic transgenerational inheritance. Previously, three generations of rats were exposed separately to vinclozolin (F0 generation), a jet fuel hydrocarbon mixture (F1 generation), and dichlorodiphenyltrichloroethane (DDT) (F2 generation), producing a transgenerational F5 generation. The current study extends this study by breeding this transgenerational F5 generation with wild-type rats to create maternal and paternal outcross lineages, labeled MOC and POC, respectively. In the current study, we examined the differential DNA methylated regions (DMRs) in the outcross F6 generation offspring to detect potential parent-of-origin lineage‑specific inheritance impacts. When comparing both outcross MOC and POC lineages of the F6 generation to a control outcross F3 generation from the same lineage, with no toxicant exposure, a higher number of DMRs were observed in the F6 generation lineages. Additionally, while there was some common overlap between the two MOC and POC outcross generations, only the F6 POC generation had overlaps with the F5 multigenerational exposure lineage generation of the previous study, which was also a paternal outcross. Since previous pathology analysis has been extensive, limited pathology (e.g. obesity) was performed in the current study to primarily confirm the transgenerational pathology in the F6 generation outcross lineages. Comparisons between the control same lineage F3 generation and both of the outcross F6 generations identified outcross‑specific results, suggesting sex-specific epigenetic inheritance after ancestral toxicant exposure. Therefore, both the oocyte and sperm facilitate epigenetic transgenerational inheritance.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"21 1","pages":"2719246"},"PeriodicalIF":3.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13502001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging roles of RNA N5-methylcytosine modification in reproductive physiology and gynecological diseases.","authors":"Fei Lv, Yi Jin, Shuchen Yu, Xinyi Yang, Shiyu Xia, Xiaoye Ye, Qihang Zhao, Ying Hu, Aolin Zheng, Yongfeng Wu, Jinyi Tong","doi":"10.1080/15592294.2026.2629068","DOIUrl":"10.1080/15592294.2026.2629068","url":null,"abstract":"<p><p>The epitranscriptome, comprising post-transcriptional RNA modifications, has emerged as a pivotal regulator of gene expression in the female reproductive system. Among these modifications, 5-methylcytosine (m5C) stands out as a widespread and highly conserved mark whose roles in female reproductive health and disease are increasingly recognized but have not yet been systematically summarized. This review aims to synthesize current knowledge on the functions and regulatory mechanisms of m5C in female reproductive physiology and associated pathologies. We begin with a foundational overview of m5C, detailing its definition, biological functions, and the dynamic regulatory network of 'writers,' 'readers,' and 'erasers.' We then examine the critical roles of m5C in key physiological processes, including oogenesis and early embryonic development. Furthermore, we provide an in-depth analysis of the mechanistic involvement and clinical implications of m5C dysregulation in various gynecological diseases. By consolidating recent advances, this review seeks to establish a comprehensive framework for understanding m5C in the female reproductive system and to offer a valuable reference and theoretical basis for future research and therapeutic exploration.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"21 1","pages":"2629068"},"PeriodicalIF":3.7,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12962712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147354462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient elevation in cellular glucose uptake exacerbates pressure overload-induced cardiac hypertrophy and dysfunction.","authors":"Sayan Bakshi, Samuel F Chang, Luke A Potter, Zhihuan Sun, Chae-Myeong Ha, Kerstin Preuss, Mahima S Reddy, Caitlin A Harrell, John C Chatham, Adam R Wende","doi":"10.1080/15592294.2026.2638670","DOIUrl":"10.1080/15592294.2026.2638670","url":null,"abstract":"<p><p>Clinically prior hyperglycemia may lead to long-lasting adverse cardiovascular effects, a process referred to as 'glycemic memory.' Epigenetic modifications, specifically DNA methylation changes, may play a key role in this phenomenon. This study investigated if prior high glucose delivery to cardiomyocytes, led to worsened cardiovascular effects upon pressure overload and to ascertain the gene expression and corresponding DNA methylation signatures linked to glycemic memory. Using inducible and cardiomyocyte-specific glucose transporter 4 (GLUT4) overexpressing mice. We induced glucose delivery for 2 weeks, then returned to basal uptake for 2 weeks, followed by sham or transverse aortic constriction (TAC) surgery as a secondary stress. Mice were followed for an additional 8 weeks and assessed for contractile function, cellular remodeling, and molecular changes. TAC led to an exacerbated hypertrophic response and cardiac dysfunction in the transgenic mice. Subsequent analysis identified molecular changes akin to heart failure, worsened cardiac fibrosis, and oxidative stress. Using bulk RNA-sequencing and reduced representation bisulfite sequencing, we discovered differential gene expression and DNA methylation signatures that persisted even after cellular glucose levels reverted to normal. Significant changes across both expression and methylation-identified enriched pathways related to adverse cardiac events, supporting a glycemic memory response. Glycemic memory led to cardiac structural and functional exacerbation, mimicking heart failure, when subjected to a secondary stress. Our data identified transcriptome, and preliminary DNA methylome changes which may potentially be molecular signatures of future therapeutic targets associated with this heart failure susceptibility resulting from enhanced glucose delivery.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"21 1","pages":"2638670"},"PeriodicalIF":3.7,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12962670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147354408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>NOS1</i> hypermethylation may participate in the colorectal cancer development and be associated with its prognosis.","authors":"Zhaohui Zhang, Aibuta Yeerken, Xinyao Shao, Sangni Qian, Shujuan Lin, Simeng Gu, Xiaojiang Ying, Zhenjun Li, Xinglin Fei, Jinhua Yang, Mengling Tang, Jianbing Wang, Mingjuan Jin, Kun Chen","doi":"10.1080/15592294.2026.2660022","DOIUrl":"10.1080/15592294.2026.2660022","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Although epigenetic alterations are common in CRC, the epigenetic changes that occur during colorectal carcinogenesis remain unclear. Thus, we sought to elucidate the role of <i>NOS1</i> methylation in colorectal carcinogenesis, which is essential for understanding disease pathology. We used the UCSC Xena database to comparatively analyze <i>NOS1</i> expression and methylation status between tumour and adjacent normal tissues across 33 cancer types. Low expression and hypermethylation of <i>NOS1</i> have been identified in 12 cancer types, with CRC demonstrating this characteristic epigenetic regulation. <i>NOS1</i> promoter methylation status was examined using genomic DNA extraction and MassARRAY EpiTYPER methylation analysis. <i>NOS1</i> hypermethylation was confirmed among CRCs in in-house dataset 1 (<i>p</i> < 0.001), and among CRCs and advanced adenomas in in-house dataset 2 (<i>p</i> < 0.001). An upward trend in methylation changes was identified from non-advanced adenoma to advanced adenoma to CRC (<i>p</i> for trend < 0.001). Quantitative real-time PCR was used to analyze <i>NOS1</i> expression in in-house Dataset 3, and significantly low <i>NOS1</i> expression was also identified in CRCs (<i>p</i> < 0.001). Kaplan-Meier estimator and Cox proportional hazard models were used to assess the prognostic and predictive roles of <i>NOS1</i>. <i>NOS1</i> hypermethylation was significantly associated with better disease-specific survival (DSS) in CRC patients. <i>NOS1</i> hypermethylation is an epigenetic driver of colorectal tumorigenesis and is associated with better survival.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"21 1","pages":"2660022"},"PeriodicalIF":3.7,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13128025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune pathways and prenatal/perinatal environmental exposures contribute to epigenetic gestational age prediction and acceleration.","authors":"Amy A Eapen, Ian M Loveless, Mingming Pan, Xiaoyu Liang, Audrey Urquhart, Jennifer K Straughen, Andrea E Cassidy-Bushrow, Alexandra R Sitarik, Neil Simmerman, Emma Thompson, Leah Kottyan, Carole Ober, Christine C Johnson, Edward Zoratti, Albert M Levin","doi":"10.1080/15592294.2025.2610521","DOIUrl":"10.1080/15592294.2025.2610521","url":null,"abstract":"<p><p>DNA methylation (DNAm), capturing chronological gestational age (GA) and epigenetic gestational age acceleration (EGAA), can be modified by environmental exposures. The Asthma&Allergy array is a new DNAm array developed with content focused on asthma and allergy loci. The association between content on the Asthma&Allergy array and chronological GA and EGAA has not been evaluated alone or in the context of prenatal/perinatal exposures. We performed an epigenome wide association study (EWAS) chronological GA at single CpG sites and regions in cord blood from 391 newborn children from a Detroit-based birth cohort. We further constructed a multi-CpG site methylation model to predict chronological GA. Also, associations between prenatal/perinatal environmental factors with GA, epigenetic gestational age (EGA), and EGAA were assessed. We identified 2,435 CpG sites associated with chronological GA, and CpGs within the HLA class II locus (<i>HLA-DRB1, HLA-DQB1, HLA-DRB6</i>) were among the most significantly associated with chronological GA. Our multi-CpG site model attained higher predictive accuracy (R² = 0.88) comparable to other published methods. Using genes implicated in region-based analyses (<i>n</i> = 395 regions), the pathways most significantly enriched with chronological GA-associated CpGs included T helper 1(Th1) and 2(Th2) activation, B-cell development, and IL-10 signaling, which were also enriched in at least one of the other published epigenetic GA clocks. In multi-exposure models, infant's first-born status and maternal parity were associated with EGAA. Our findings highlight enrichment for T cell modulated pathways and antigen presentation as biological processes associated with chronological GA, as well as prenatal/perinatal factors that may affect EGAA.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"21 1","pages":"2610521"},"PeriodicalIF":3.7,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146009084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"m6A methylation of circKPNA2 promotes colorectal carcinogenesis by activating the RIN1-Ras pathway.","authors":"Jinhai Tian, Zongying Jiang, Qi Huang, Jia Wang, Yaqin He","doi":"10.1080/15592294.2026.2672219","DOIUrl":"10.1080/15592294.2026.2672219","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a prevalent and highly lethal malignancy. However, the molecular mechanisms underlying its progression remain incompletely understood. Therefore, this study aimed to investigate the role and mechanisms of circKPNA2 in CRC progression. We used various techniques, including RNA sequencing, functional assays, RNA pull-down, and mass spectrometry, to examine the expression and function of circKPNA2. Our findings indicate that circKPNA2 is significantly upregulated in CRC tissues and cell lines. It contributes to tumour growth by promoting cell proliferation, migration, and invasion. We found that circKPNA2 specifically binds to the RIN1 protein and increases its levels, thereby activating the Ras signalling pathway and facilitating CRC progression. Additionally, we identified that METTL3 regulates the expression of circKPNA2 through N6-methyladenosine (m⁶A) methylation, which in turn affects CRC cell proliferation, migration, and invasion. These results deepen our understanding of CRC biology and underscore the potential of targeting circKPNA2 as both a therapeutic target and a diagnostic biomarker to improve CRC diagnosis and treatment.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"21 1","pages":"2672219"},"PeriodicalIF":3.7,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13285648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 role of <i>trans</i>-acting factors in the pathogenesis of common psychiatric disorders.","authors":"Jacob Peedicayil, Dennis R Grayson","doi":"10.1080/15592294.2026.2644747","DOIUrl":"10.1080/15592294.2026.2644747","url":null,"abstract":"<p><p>According to the omnigenic model for the inheritance of common traits proposed by Jonathan Pritchard's group in 2017, there are a very large number of genetic variants underlying common traits spread across the genome. Causal variants are of two types: core genes that have direct roles in disease pathogenesis that contribute only a small amount to total heritability and peripheral genes that are much more in number than core genes and that cumulatively contribute maximally to trait heritability. The same group proposed in 2019 that peripheral genes have indirect effects by acting in <i>trans</i>. The authors propose that most heritability is due to weak <i>trans</i>-expression quantitative trait loci (<i>trans</i>-eQTL) single nucleotide polymorphisms (SNPs) whose effects are mediated by peripheral genes that influence the expression of core genes. In 2018, we provided evidence for an epigenetic-based omnigenic model for the inheritance of common psychiatric disorders. In the current article, we discuss the possible role of genes underlying <i>trans</i>-acting factors, namely, non-coding RNAs and transcription factors, in the pathogenesis of common psychiatric disorders.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"21 1","pages":"2644747"},"PeriodicalIF":3.7,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13048609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA <i>Dlx4os</i> drives malignant transformation and phenotype switching in melanoma.","authors":"Ana Luisa Pedroso Ayub, Beatriz Cristina Biz Tonin, Hátylas Azevedo, Pedro Henrique Fogaça Jordão, Tanvi Saxena, Leinal Sejour, Jeremie Nsengimana, Ioannis Vlachos, Eduardo Moraes Reis, Frank John Slack, Miriam Galvonas Jasiulionis","doi":"10.1080/15592294.2026.2641924","DOIUrl":"10.1080/15592294.2026.2641924","url":null,"abstract":"<p><p>Cutaneous melanoma, a highly aggressive and therapy-resistant skin cancer, is characterized by its remarkable cellular plasticity, enabling tumour cells to switch between different phenotypic states. This plasticity contributes to tumour heterogeneity and is regulated by key transcription factors. Long non-coding RNAs (lncRNAs) are emerging as crucial regulators in melanoma progression, yet much remains to be explored regarding their role in phenotype switching. In this study, we analysed long non-coding RNAs (lncRNAs) across different murine melanoma cell lines, identifying a set of lncRNAs potentially involved in regulating melanoma phenotypic state through cis-regulation of neighbouring protein-coding genes. We demonstrated that the lncRNA <i>Dlx4os</i> regulates genes associated with melanoma plasticity, favouring a mesenchymal-like, undifferentiated state. <i>Dlx4os</i> knockdown redirected melanoma cells to a more differentiated and less malignant phenotype, confirmed by differential expression of phenotypic state markers (<i>Sox10, Mitf, Tgfβ, Sox6, Mlana</i>), reduced their invasive and migratory potential, and delayed tumour progression <i>in vivo</i>. Furthermore, we identified a human orthologue of <i>Dlx4os</i>. Our findings highlight the potential of <i>Dlx4os</i> as both a biomarker and therapeutic target, capable of modulating melanoma's phenotypic plasticity to influence treatment response and metastasis.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"21 1","pages":"2641924"},"PeriodicalIF":3.7,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13003849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147485021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}