Epigenomes最新文献

{"title":"CpG Methylation of Protein Prenyltransferase Genes <i>FNTA</i>, <i>FNTB</i>, <i>PGGT1B</i> and <i>RABGGTA</i> in Cancer Cell Lines.","authors":"Dominik Jung, Daniel Diehl, Anna Hagemann, Hagen Sjard Bachmann","doi":"10.3390/epigenomes10010017","DOIUrl":"10.3390/epigenomes10010017","url":null,"abstract":"<p><p><b>Background:</b> Protein prenylation is crucial for the function of hundreds of proteins. Aberrant protein prenylation can be caused by the aberrant expression of prenyltransferases (PTases), which has been reported for multiple cancer entities. The reasons for aberrant PTase expression in cancer have not yet been investigated. <b>Methods:</b> We analyzed CpG methylation within promoter-associated CpG islands of the PTase genes <i>FNTA</i>, <i>FNTB</i>, <i>PGGT1B</i>, and <i>RABGGTA</i> via bisulfite conversion and pyrosequencing to assess its role in PTase expression and gain deeper insight into the regulation of protein prenylation in cancer. We used DNA from three benign controls (whole blood samples, peripheral blood mononuclear cells, and HEK293) and 19 human cancer cell lines from various origins to assess DNA methylation within PTase gene promoter-associated CpG islands. For a subset of these cell lines, we measured mRNA expression via qPCR and correlated it with DNA methylation. <b>Results:</b> Methylation across all PTase genes ranged from 1.9 ± 0.9% to 11.4 ± 4.0% (mean methylation ± standard deviation) in benign cells, and 2.3 ± 1.0% to 16.0 ± 5.4% in cancer cells. DNA methylation and mRNA expression of <i>PGGT1B</i> correlated inversely (PCC = -0.75; <i>p</i> = 0.005). <b>Conclusions:</b> We saw no general differences between benign and malignant cells, but observed significant differences between non-malignant controls and multiple individual cancer cell lines regarding the methylation of PTase genes. This was prominently seen in <i>PGGT1B</i> in Caki-1 cells, raising the possibility that DNA methylation is involved in the dysregulation of PTase expression in cancer.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13025263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147534450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Analysis Reveals Conserved R-Loop Features in Mouse Embryonic Stem Cells.","authors":"Ohbeom Kwon, Hyeonwoo La, Seonho Yoo, Hyeonji Lee, Heeji Lee, Hoseong Lim, Chanhyeok Park, Dong Wook Han, Jeong-Tae Do, Hyuk Song, Youngsok Choi, Kwonho Hong","doi":"10.3390/epigenomes10010016","DOIUrl":"10.3390/epigenomes10010016","url":null,"abstract":"<p><p>R-loops, three-stranded nucleic acid structures formed by an RNA-DNA hybrid, have emerged as important regulators of transcription and genome stability. Although advances in high-throughput sequencing have revealed widespread R-loop landscapes, platform-specific biases hinder the identification of conserved R-loops in specific cell types. Mouse embryonic stem cells, which are transcriptionally active, provide an ideal system for investigating the potential roles of stable R-loops in RNA biology. Here, we integrated 13 independent R-loop profiling datasets from four experimental platforms to define 27,950 Common R-loop regions in mouse embryonic stem cells and characterized their chromatin environment and associated biological functions. Common R-loop regions were reproducibly detected across methods and were preferentially localized to promoter-proximal and genic regions enriched in CpG islands. Genes associated with Common R-loops were highly and stably expressed, showing strong functional enrichment in RNA metabolic processes such as mRNA processing, RNA splicing, and ribonucleoprotein complex biogenesis. Chromatin state analysis revealed that Common R-loops are enriched in transcriptionally active and regulatory contexts. Sequence feature analysis further identified GC skew as a prominent signature of Common R-loops, particularly within transcribed chromatin states. Transcription factor motif analyses have identified distinct regulatory environments in Common R-loop regions, including pluripotency-associated OCT4-SOX2-TCF-NANOG motifs in enhancers, CTCF motifs in open chromatin, and YY1 motifs in promoters. Together, this study provides the first integrated analysis of conserved R-loop regions in mouse embryonic stem cells, revealing their preferential localization at regulatory loci linked to RNA metabolism and highlighting R-loops as structural and functional nodes in RNA biology.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13025856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147534373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone Modifications in the Cell Cycle of <i>C. elegans</i> Embryogenesis: A Comparative Review.","authors":"Anati Alyaa Azhar, Hector Mendoza","doi":"10.3390/epigenomes10010015","DOIUrl":"10.3390/epigenomes10010015","url":null,"abstract":"<p><p>Cell division is a highly regulated process that actively involves dynamic changes to the genetic material within the nucleus. DNA is faithfully replicated in the S-Phase of the cell cycle, being converted from loose, relaxed chromatin into tight, condensed chromosomes to be segregated in mitosis. In addition to scaffolding proteins that shape these mitotic chromosomes, post-translational modifications of histones within nucleosomes modulate chromosome dynamics throughout the cell cycle. In this review, we use a comparative approach to highlight some of the major epigenetic marks affected by the cell cycle during embryogenesis of <i>Caenorhabditis elegans</i>: H4K20me1, H3S10ph, H4S1ph, H2AS1ph, and H3T118ph. These five histone post-translational modifications will be specifically highlighted in the context of the mitotic cell cycle, as they are well documented in the <i>C. elegans</i> literature.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13025373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147534413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Activity of Cancer Therapy Drugs Revealed by HeLa TI Cell-Based Assay.","authors":"Varvara Maksimova, Valeriia Popova, Alyona Kholodova, Julia Makus, Olga Usalka, Eugenia Lylova, Aleksandr Kudriashov, Gennady Belitsky, Marianna Yakubovskaya, Kirill Kirsanov","doi":"10.3390/epigenomes10010014","DOIUrl":"10.3390/epigenomes10010014","url":null,"abstract":"<p><strong>Background/objectives: </strong>The aberrant epigenetic landscape of cancer cells has attracted wide attention, motivating the search for new epigenetically active drugs both for anticancer therapy and for overcoming the drug resistance promoted by epigenetic changes. The use of epi-drugs in cancer therapy requires consideration of the influence of applied treatment on epigenetic regulation of gene expression. Therefore, it is reasonable to screen epigenetically active compounds among the drugs widely used in clinical oncology.</p><p><strong>Methods: </strong>We applied the HeLa TI cell-based assay to analyze the epigenetic activity of 40 drugs including 22 chemotherapeutic, 2 immunotherapeutic, 13 targeted, and 3 palliative agents. Reactivation of the epigenetically silenced <i>GFP</i> reporter gene integrated into the genome of HeLa TI cells was assessed using flow cytometry.</p><p><strong>Results: </strong>Statistically significant increases in the proportions of GFP-positive cells were demonstrated for the alkylating agent chlorambucil; the antimetabolites cytarabine, fluorouracil, gemcitabine, and pemetrexed; the platinum-based compounds cisplatin, and oxaliplatin; the topoisomerase inhibitor topotecan; and the antimicrotubule agents docetaxel, vincristine, and eribulin. Epigenetic activity was also detected for the targeted-therapy agents AZD8055, wortmannin, and cetuximab, as well as for the corticosteroid dexamethasone. Thus, epigenetic activity was revealed for 15 drugs widely used in cancer therapy, which possess different modes of action.</p><p><strong>Conclusions: </strong>Our findings show that many anticancer therapy agents modulate the epigenetic landscape of cancer cells, providing a rationale for expanding their therapeutic applications and enhancing the efficacy of combination strategies by overcoming epigenetically driven chemoresistance.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13025751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147534432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Epigenetic Battleground: Host Chromatin at the Core of Infection.","authors":"Fabrício Castro Machado, Nilmar Silvio Moretti","doi":"10.3390/epigenomes10010013","DOIUrl":"10.3390/epigenomes10010013","url":null,"abstract":"<p><p>Chromatin dynamics are usually modulated by histone epigenetic post-translational modifications, which rapidly and reversibly govern accessibility and transcriptional responsiveness. During microbial infection, this regulatory layer becomes a highly contested interface where host defense mechanisms and pathogen-driven subversion strategies converge and compete. Many infectious agents exploit chromatin to reprogram gene expression, creating cellular environments that are conducive to infection, proliferation, and persistence. Diverse strategies have been described for viruses, bacteria, fungi, protozoa and nematodes, including the direct secretion of acetyltransferases and methyltransferases, interference with host chromatin-binding proteins, subcellular localization of transcriptional factors or epigenetic regulators, and metabolic availability manipulation. Concurrently, host cells activate immune and stress-response genes to mount rapid, adaptable antimicrobial responses. Recent advances in genome-wide, single-cell, and spatial omics profiling have begun to reveal the temporal and cell-type-specific dynamics of the host genome at the core of infection. This review synthesizes current insights into how chromatin is rewired by the major categories of pathogens during infection, highlighting representative case studies across infective agents and the functional consequences for immunity and cell fate. In addition, we discuss emerging techniques for epigenomic and transcriptomic data collection, and the potential of targeted host-directed therapeutic strategies. Chromatin regulation is thus a promising field of study and a possible target for next-generation interventions.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12937675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preliminary Evidence of Blood DNA Methylation Changes in Pregnant Women Adhering to a Mediterranean Diet.","authors":"Grace Tavelli, Nikki Schultz, Joanna Brisbane, Nina Kresoje, Samantha Lodge, Jeremy K Nicholson, Nicola J Armstrong, Desiree Silva, Nina D'Vaz, David Martino","doi":"10.3390/epigenomes10010012","DOIUrl":"10.3390/epigenomes10010012","url":null,"abstract":"<p><strong>Background/objectives: </strong>Consumption of a Mediterranean diet (MD) has been associated with reduced incidence of non-communicable diseases and reduced overall mortality, with epigenomic effects representing plausible mediators. The aim of this pilot study was to explore potential epigenetic associations between DNA methylation markers in blood and adherence to an MD in pregnancy.</p><p><strong>Methods: </strong>Fifty-two pregnant women with high or low adherence to an MD throughout pregnancy, who participated in the BioMood ORIGINS study, were selected using an extremes-of-exposure design. DNA methylation (DNAm) profiles from whole blood were generated using the TWIST human methylome panel. We conducted both genome-wide and candidate gene-based differential methylation analyses to identify epigenetic variations between the study groups. Furthermore, we explored potential associations between blood methylation patterns and circulating inflammatory markers (GlycA, GlycB and SPC) previously observed to exhibit differential abundance in the same cohort of women.</p><p><strong>Results: </strong>There were no genome-wide significant differences in methylated dinucleotides between MD groups (<i>p</i>-value < 5 × 10^-8); however, a region-based analysis identified 2210 differentially methylated regions (DMRs) (FDR < 0.05, absolute maximum logFC > 1) annotated to 1537 genes, significantly enriched in metabolic, inflammatory and neuronal signaling pathways. Leveraging publicly available data, we replicated nine novel DMR associations. Changes in circulating phospholipid inflammatory markers were significantly associated with a small methylation difference in Lipin-1 (<i>LPIN1)</i>, albeit with a small effect size (<i>p</i>-value < 5 × 10^-8). A look-up analysis of previously reported MD-associated genes in this cohort detected small but statistically significantly different methylation of CpGs located within collagen type XVIII alpha 1 (<i>COL18A1)</i> and peroxisome proliferator-activated receptor gamma, coactivator 1 beta (<i>PPARGC1B)</i> gene regions.</p><p><strong>Conclusions: </strong>We provide preliminary evidence for modest methylation changes in specific genes associated with adherence to an MD.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12921938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of HERV-K (HML2) Expression in Colorectal Cancer Samples.","authors":"Valentina S Obrezanenko, Polina M Shulga, Anastasia G Volkova, Anastasia A Primova, Yulia A Remizova, Ivan O Meshkov, Alexandra D Kikot, Daria A Tarasova, Ekaterina S Bolashova, Alexey A Ivashechkin, Antonida V Makhotenko, Ekaterina A Snigir, Yulia A Masyukova, Elizaveta I Radion, Olesya A Kuznetsova, Maria S Cheporova, Michail Y Fedyanin, Alexey A Tryakin, Valentin V Makarov, Vladimir S Yudin, Anton A Keskinov, Anna S Makarova","doi":"10.3390/epigenomes10010011","DOIUrl":"10.3390/epigenomes10010011","url":null,"abstract":"<p><strong>Background: </strong>HML-2 subgroup mobile genetic elements of the HERV-K family were described to participate in carcinogenesis processes, but their expression and epigenetic regulation in molecular subtypes of colorectal cancer (CRC) remain partly characterized. The present study aimed to evaluate the expression of HML-2 elements using RNA-sequencing data in paired tumor and normal intestinal tissue samples from 63 patients with CRC to identify patterns of the retrotransposons' activity in different molecular subtypes (CMSs).</p><p><strong>Methods: </strong>RNA-sequencing and DNA methylation data were analyzed for paired CRC and normal tissue samples. HERV-K expression was assessed using three bioinformatics tools: Telescope (version 1.0.3), TEtranscripts (version 2.2.3), GeneTEFlow (version 2020). Molecular tumor subtypes were defined using the CMScaller (version 0.99.2) program. The results of the HML-2 loci expression analysis were supplemented with the HML-2 proteins expression data obtained by quantitative RT-PCR.</p><p><strong>Results: </strong>HML-2 expression assessment by GeneTEFlow (version 2020), TECount (version 2.2.3) and Telescope (version 1.0.3) showed high convergence: the Pearson correlation coefficient for each tool exceeded 0.88. Several HML-2 loci were identified as differentially expressed in CRC samples of different CMS. The PCR results confirmed an increase in HML-2 expression in tumor tissues. For all CMSs, an inverse association was detected between differential methylation of CpG sites and differential expression of HML-2 loci. Associations of HML-2 expressions with differentially expressed genes in which they are located were found, and for a number of such genes an inverse relationship between the expression level and the methylation level of their promoters were demonstrated, and data on the involvement in the pathogenesis of CRC were described: <i>CR1</i>, <i>CD48</i>, <i>TTLL3</i>, <i>ABCC2</i> and <i>ZNF420</i>. Expression signatures associated with the activity of the RIG-I-like receptor signaling cascade were identified in CMS1-3 CRC samples, which may indicate the possible implementation of viral mimicry against the background of HML-2 activation.</p><p><strong>Conclusions: </strong>Analysis of the expression of HML-2 and its association with CpG methylation contributes to a comprehensive interpretation of the CRC pathogenesis mechanisms.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12922068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic-Epigenetic Interplay in Epilepsy: Pathways, Biomarkers, and Epigenome-Targeted Therapies.","authors":"Andra-Giorgiana Zaruha, Patricia Codreanu, Mădălin-Codruț Coman, Monica Andreea Novac Ii, Simona Gabriela Duță-Ion, Ioana Ruxandra Jugănaru, Iulian Andrei Hotinceanu, Andra Dan, Livia Mălina Burtavel, Anca-Elena Eftenoiu, Diana Bârcă, Andreea Ionescu, Cerasela Paraschiv, Viorica-Elena Rădoi","doi":"10.3390/epigenomes10010010","DOIUrl":"10.3390/epigenomes10010010","url":null,"abstract":"<p><p>Epilepsy is a heterogeneous neurological disorder with a strong genetic basis, yet recent evidence underscores the critical role of epigenetic mechanisms in its pathogenesis. This review synthesizes current knowledge on how chromatin remodeling, histone modifications, DNA methylation, and transcriptional regulation intersect with classical channelopathies and signaling pathways. We emphasize how epigenetic dysregulation contributes to neuronal excitability and network plasticity, particularly through interactions with mTOR, PI3K-AKT, and GABAergic signaling cascades. The convergence of genetic mutations and epigenetic modifications creates a dynamic landscape in which environmental factors can modify gene expression and contribute to the development of epilepsy. Emerging therapeutic strategies-including epigenetic drugs (HDAC inhibitors, DNMT inhibitors), CRISPR/dCas9-based epigenome editing, and multi-omics approaches-offer promising avenues for precision medicine. This review provides a comprehensive synthesis of genetic and epigenetic mechanisms in epilepsy, examining how these layers interact to produce disease phenotypes and discussing the therapeutic implications of this multilayered regulation.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12921879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Liquid Biopsy Marks Atrial Fibrillation: Evidence from the AF Big Picture Study.","authors":"Riccardo Proietti, Nicola Tidbury, Joshua Preston, Maanya Vittal, Philippa McCabe, Garry McDowell, Gregory Y H Lip, Manlio Vinciguerra","doi":"10.3390/epigenomes10010009","DOIUrl":"10.3390/epigenomes10010009","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Atrial fibrillation (AF) is currently the most common arrhythmia worldwide, and it is linked to increased mortality and morbidity, hence the need for a better clinical stratification of AF patients. Histone complexes or nucleosomes, released into the blood circulation, are found elevated in acute conditions such as stroke, trauma, and sepsis. The aim of this pilot single-centre study was to assess whether circulating histone levels could be used for diagnostic purposes in patients with AF. <b>Methods</b>: A total of 40 patients, well characterised for their biochemical and clinical characteristics, were recruited from outpatient clinics. Patients were randomly recruited into two groups (n = 20 per group), i.e., persistent AF and hypertensive controls. A multi-channel flow imaging methodology based on ImageStreamX was used with a well-optimised protocol to image and quantify five individual histones (H2A, H2B, H3, H4, and macroH2A1.1) together with the dimers (H2A/H2B, and H3/H4). <b>Results</b>: In the AF groups, plasma levels of histone dimers H2A/H2B and H3/H4 were elevated compared to hypertensive controls, 1.8% vs. 1.06% (<i>p</i>-value = 0.03). H2A/H2B dimer levels were increased in AF patients irrespective of gender, smoking status, diabetes, and pharmacological therapy. In the overall population, an inverse correlation between H2A and BMI was detected. <b>Conclusions</b>: Our pilot study, although limited in sample size, suggests that circulating histone complexes may be epigenetic sentinels for AF, offering mechanistic insights while addressing unmet needs in risk stratification.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12922129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in MicroRNA Expression in Firefighters Responding to a Train Derailment and Fire in East Palestine, Ohio.","authors":"Jaclyn M Goodrich, Yaodong Xin, Shawn C Beitel, John Gulotta, Lu Wang, Bhavya Thotakura, Judith M Graber, Derek Urwin, Alexander C Mayer, Sara Jahnke, Derrick L Edwards, Casey Grant, Sreenivasan Ranganathan, Jefferey L Burgess","doi":"10.3390/epigenomes10010008","DOIUrl":"10.3390/epigenomes10010008","url":null,"abstract":"<p><p><b>Background/Objectives</b>: High-risk, low-frequency incidents such as building collapses and large chemical fires can result in acute, high-dose exposures to toxic agents for first responders and the surrounding community. While these exposures may last for hours to days, their contribution to firefighters' risks for cancer and other diseases is relatively unknown. In February 2023, a freight train transporting chemicals derailed and caught fire in East Palestine, Ohio, US. More than 350 firefighters, primarily volunteer, responded to the incident. In this cross-sectional study, we evaluated epigenetic markers of toxicity in responding firefighters. We hypothesized that exposures from responding to the train derailment would alter the expression of microRNAs (miRNAs) linked to carcinogenesis. <b>Methods</b>: We enrolled 62 responding firefighters and a comparison group of 26 firefighters from the same region who did not respond to the incident. We measured the relative expression of 800 miRNAs in blood samples using the nCounter Human v3 miRNA expression panel. We compared the expression of miRNA between exposure groups in negative binomial regression models, adjusting for potential confounders. <b>Results</b>: At a false discover rate cut-off of 5% (q-value < 0.05), 16 miRNAs had significantly higher expression and one significantly lower among firefighters that responded to the incident. Top disease-related pathways in which these miRNAs were enriched included those relevant to neurodegenerative diseases, vascular disease, and multiple cancer sites. <b>Conclusions</b>: Overall, results suggest responding to one large incident can have non-transient impacts on miRNA expression. Whether this translates into longer-term health risks or adaptive responses to exposures is unclear.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12921792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}