Epigenomics最新文献_第6页

Epigenetic landscape of Leishmania-host interactions. 利什曼原虫与宿主相互作用的表观遗传景观。

IF 2.6 4区医学

Epigenomics Pub Date : 2025-12-01 Epub Date: 2025-10-16 DOI: 10.1080/17501911.2025.2574836

Shweta Khandibharad, Shailza Singh

{"title":"Epigenetic landscape of Leishmania-host interactions.","authors":"Shweta Khandibharad, Shailza Singh","doi":"10.1080/17501911.2025.2574836","DOIUrl":"10.1080/17501911.2025.2574836","url":null,"abstract":"Leishmaniasis is a complex immuno-metabolic infectious disease regulated by epigenetic mechanisms in both the parasite and host. Epigenetic modifications such as chromatin remodeling, histone post-translational modifications (PTMs), and non-coding RNAs (ncRNAs) modulate gene expression to promote parasite survival and alter host immune responses. This review highlights species-specific epigenetic changes across Leishmania species contributing to pathogenesis and explains how the parasite manipulates host immune signaling through epigenetic pathways, including co-infection and co-morbidity models. Host factors like nuclear factor of activated T cells 5 (NFAT5) and Src homology 2 domain-containing phosphatase-1 (SHP-1), along with parasite-derived proteins such as Su(var)3-9, enhancer of zeste [E(z)], trithorax (SET) proteins, and histones, are emerging as promising epigenetic therapeutic targets. Furthermore, histone PTMs and transcription factors are critical epigenetic modifications supporting parasite survival. Synthetic gene circuits can modulate host and parasite epigenomes. Synthetic biology enables the assembly of genetic parts and pools to engineer cells with novel biological functions. A structured literature review using Web of Science, PubMed, and Scopus was performed, using keywords like epigenetics of Leishmania, epigenetics alterations in host with leishmaniasis, Leishmania and comorbidity and disease-specific terms. This review underscores the future potential of epigenetics and synthetic biology-based strategies in controlling leishmaniasis.","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"1479-1494"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epigenetic regulation of MMP-11 and -16 expression in human prostate cancer: the role of KDM6A. 人前列腺癌中MMP-11和-16表达的表观遗传调控：KDM6A的作用

IF 2.6 4区医学

Epigenomics Pub Date : 2025-12-01 Epub Date: 2025-11-10 DOI: 10.1080/17501911.2025.2586858

Gökçe Yıldırım-Buharalıoğlu, Recep İlhan, Yaren Çakmak, C Kemal Buharalıoğlu

{"title":"Epigenetic regulation of MMP-11 and -16 expression in human prostate cancer: the role of KDM6A.","authors":"Gökçe Yıldırım-Buharalıoğlu, Recep İlhan, Yaren Çakmak, C Kemal Buharalıoğlu","doi":"10.1080/17501911.2025.2586858","DOIUrl":"10.1080/17501911.2025.2586858","url":null,"abstract":"Aims: Matrix metalloproteinases (MMPs) promote prostate cancer (PCa) progression by degrading the extracellular matrix and enhancing metastasis. PCa is considered an \"epigenetic catastrophe\" due to disrupted histone modifications caused by chromatin-modifying enzyme dysregulation. We previously showed that lysine demethylase 6A (KDM6A) and 6B (KDM6B) are higher in metastatic PCa (LNCaP) versus benign prostatic hyperplasia (BPH-1). We investigated whether their elevation contributes to MMP upregulation.Methods and results: LNCaP cells were treated with the KDM6 inhibitor GSK-J4, and mRNA levels of 23 MMPs were quantified by RT-qPCR. GSK-J4 reduced mRNA levels of 6 MMPs (MMP-7, -8, -11, -15, -16, and -19) out of 23. Decline in pre-spliced mRNA levels of MMP-7, -11, and -16 by GSK-J4 suggested transcriptional changes; only MMP-11 and -16 exhibited corresponding protein decreases. Among downregulated MMPs, MMP-7, -11, -15 and -16 mRNA were higher in LNCaP versus BPH-1, confirmed at protein level for MMP-11 and -16. KDM6A - but not KDM6B - siRNA reduced MMP-11 and -16 expression. GSK-J4 increased histone3 lysine27 trimethylation (H3K27me3) enrichment at MMP-11 and -16 promoters, as shown by Chromatin Immunoprecipitation (ChIP).Conclusion: KDM6A demethylates H3K27me3 at MMP-11 and -16 promoters, sustaining their enhanced expression in PCa and revealing a novel epigenetic mechanism driving metastasis-associated protease expression.","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"1367-1380"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145481109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrating gut microbiome and host transcriptomics for the personalized management of IBD. 整合肠道微生物组和宿主转录组学用于IBD的个性化管理。

IF 2.6 4区医学

Epigenomics Pub Date : 2025-12-01 Epub Date: 2025-11-21 DOI: 10.1080/17501911.2025.2591594

Darragh Barry, Cassandra Thachuk, Jackie Trink

{"title":"Integrating gut microbiome and host transcriptomics for the personalized management of IBD.","authors":"Darragh Barry, Cassandra Thachuk, Jackie Trink","doi":"10.1080/17501911.2025.2591594","DOIUrl":"10.1080/17501911.2025.2591594","url":null,"abstract":"Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), affects an estimated 6.8 million individuals worldwide. Although biological or small molecule drug therapies can improve patient outcomes, loss of response to treatment over time remains high, highlighting the need for new precision medicine strategies. Dysbiosis of the gut microbiome is characterized by the loss of beneficial microbes and an overgrowth of pro-inflammatory pathobionts. In IBD, gut dysbiosis contributes to chronic intestinal inflammation via altered metabolite profiles and epithelial barrier disruption. Recent advancements in multi-omics integration offer approaches to better understand the pathogenesis of IBD. Epigenomic studies have revealed disease-specific DNA methylation and enhancer activation patterns that reshape immune pathways and compromise epithelial barrier integrity, key mechanisms in IBD pathophysiology. These molecular signatures allow for the stratification of IBD patients into distinct subgroups, allowing for more targeted therapeutic strategies. Here we explore the potential benefits of integrating gut microbiome and both host transcriptomics and epigenomics to improve disease management in IBD patients. While challenges remain - such as data standardization, computational complexity, and cost - the progression of multi-omics methodologies is expected to improve patient outcomes by reducing high treatment failure rates in IBD patients.","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"1503-1512"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genome-wide methylation changes upon Caco-2 cells exposure to undigested and digested titanium dioxide nanoparticles. Caco-2细胞暴露于未消化和消化的二氧化钛纳米颗粒后，全基因组甲基化变化。

IF 2.6 4区医学

Epigenomics Pub Date : 2025-12-01 Epub Date: 2025-11-25 DOI: 10.1080/17501911.2025.2593814

Célia Ventura, Ana Valente, Luís Vieira, Catarina Silva, Dora Rolo, Maria João Silva, Henriqueta Louro

{"title":"Genome-wide methylation changes upon Caco-2 cells exposure to undigested and digested titanium dioxide nanoparticles.","authors":"Célia Ventura, Ana Valente, Luís Vieira, Catarina Silva, Dora Rolo, Maria João Silva, Henriqueta Louro","doi":"10.1080/17501911.2025.2593814","DOIUrl":"10.1080/17501911.2025.2593814","url":null,"abstract":"Introduction: Titanium dioxide nanoparticles (TiO2NPs) are relevant nanomaterials (NMs) for biomedicine and industry, which raise concerns about its effects on human health, particularly through ingestion. Several studies found that exposure to NMs can lead to DNA methylation changes. DNA methylation regulates gene expression, playing a vital role in development and disease, with aberrant methylation linked to cancer and other health conditions.Aim: We aimed at identifying DNA methylation changes in intestinal cells exposed to three TiO2NPs (NM-102, NM-103, NM-105), either digested or undigested. Their cellular effects were investigated by functional pathway and gene ontology (GO) analysis.Results: 48, 41, 55 differentially methylated genes (DMG) were identified after exposure to undigested NM-102, NM-103, NM-105; 71, 65, 55 DMG in the digested counterparts. Undigested TiO2NPs affected many G-proteins/adenylate cyclase-related pathways (PKA, glucagon, GPER1, CREB1, ADORA2B); the digested had lower impact. Cancer-related pathways were shared. Enriched molecular functions were mainly transcription-related; different biological processes were enriched if TiO2NPs were digested or not.Conclusions: TiO2NPs exposure causes DNA methylation changes that have a functional impact on intestinal cells, which differs with its physicochemical properties and digestion. NM-105 caused hypermethylation, unlike the other TiO2NPs. This study highlights DNA methylation relevance in assessing NMs' toxicity.","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"1381-1397"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High level of KMT5C is associated to better prognosis and its knockdown increases proliferation in head and neck cancer. 高水平的KMT5C与更好的预后相关，其敲低可增加头颈癌的增殖。

IF 2.6 4区医学

Epigenomics Pub Date : 2025-12-01 Epub Date: 2025-12-23 DOI: 10.1080/17501911.2025.2603884

Lucas Oliveira Sousa, Gabriel da Silva, Thaís Moré Milan, Emerson de Souza Santos, Andréia Machado Leopoldino

{"title":"High level of KMT5C is associated to better prognosis and its knockdown increases proliferation in head and neck cancer.","authors":"Lucas Oliveira Sousa, Gabriel da Silva, Thaís Moré Milan, Emerson de Souza Santos, Andréia Machado Leopoldino","doi":"10.1080/17501911.2025.2603884","DOIUrl":"10.1080/17501911.2025.2603884","url":null,"abstract":"Aim: The Histone methyl transferase KMT5C/SUV4-20H2 has been described as a promising marker in several types of cancer. We investigated the impact of KMT5C knockdown on cell proliferation capacity as well as its association with clinic pathological features in HNSC patients.Methods: The relative level of KMT5C was measured by quantitative real-time PCR in HNSC lineages with high and low levels of SET/I2PP2A protein, and the cell proliferation capacity was evaluated after the knockdown of KMT5C. Furthermore, statistical tests were used to verify the association of KMT5C levels and pathological features in HNSC patients.Results: The knockdown of KMT5C decreased the levels of H4K20me2 and miR-137 while upregulating SET/I2PP2A, KI67, p-Rb, and PCNA proteins. The cell proliferation capacity of the HNSC lineage was also increased after the knockdown of KMT5C. Furthermore, the higher KMT5C level is associated with better survival, while a lower KMT5C level is associated with perineural invasion in HNSC patients.Conclusion: KMT5C levels regulate targets involved in cell proliferation and represent a potential biomarker for predicting survival and perineural invasion in HNSC.","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"1323-1333"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Emerging roles of RNA modifications in normal development and congenital craniofacial malformations. RNA修饰在正常发育和先天性颅面畸形中的新作用。

IF 2.6 4区医学

Epigenomics Pub Date : 2025-12-01 Epub Date: 2025-12-17 DOI: 10.1080/17501911.2025.2600381

Chenli Kong, Fuyi Liu, Siyue Yao, Lan Ma

{"title":"Emerging roles of RNA modifications in normal development and congenital craniofacial malformations.","authors":"Chenli Kong, Fuyi Liu, Siyue Yao, Lan Ma","doi":"10.1080/17501911.2025.2600381","DOIUrl":"10.1080/17501911.2025.2600381","url":null,"abstract":"RNA modifications represent a pivotal epitranscriptomic layer modulating gene expression beyond the classic central dogma. Increasing studies have revealed their essential roles in orchestrating mammalian development and contributing to congenital disorders. In this review, we focus on seven well-characterized RNA modifications, including N6-methyladenosine(m6A), N1-methyladenosine(m1A), 5-methylcytosine (m5C), N4-acetylcytosine (ac4C), N7-methylguanosine (m7G), pseudouridine (Ψ), and adenosine-to-inosine (A-to-I) editing, and briefly introduce emerging marks like N1-methylguanosine at position 9 (m1G9) and N2-methylguanosine (m2G). We first summarize their distribution patterns and regulatory mechanisms. Then, we examine their stage-specific functions during early embryogenesis, from fertilization to post-implantation. Further, we integrate current evidence linking RNA modifications to craniofacial development, categorized into system-associated and localized craniofacial malformations. Special attention is given to their crosstalk with chromatin dynamics and neural crest cell plasticity. Finally, we discuss their potential as environmental sensors and therapeutic targets, emphasizing the need to decode their roles in craniofacial morphogenesis. Understanding the mechanistic roles of RNA modifications in craniofacial morphogenesis opens new avenues for uncovering disease etiology, discovering diagnostic biomarkers, and designing targeted therapies. A structured literature review using PubMed and Web of Science was performed, using keywords like RNA modifications, craniofacial malformations and epitranscriptomics.","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"1601-1619"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SUV39H2 is a vulnerability in glioblastoma stem cells enhanced by co-targeting SUV39H1. SUV39H2是胶质母细胞瘤干细胞中的一种易感蛋白，通过共同靶向SUV39H1而增强。

IF 2.6 4区医学

Epigenomics Pub Date : 2025-12-01 Epub Date: 2025-10-05 DOI: 10.1080/17501911.2025.2568366

Bihui Cao, Qiqi Xie, Chunying Li, Jensen Mast, Bokai Wang, Qinyi Miao, Chafiq Hamdouchi, Timothy A Grese, Jia Shen

{"title":"SUV39H2 is a vulnerability in glioblastoma stem cells enhanced by co-targeting SUV39H1.","authors":"Bihui Cao, Qiqi Xie, Chunying Li, Jensen Mast, Bokai Wang, Qinyi Miao, Chafiq Hamdouchi, Timothy A Grese, Jia Shen","doi":"10.1080/17501911.2025.2568366","DOIUrl":"10.1080/17501911.2025.2568366","url":null,"abstract":"Aim: To investigate the role of SUV39H2 in glioblastoma (GBM) stem cells (GSCs) and assess whether co-targeting SUV39H2 and SUV39H1 more effectively disrupts GSC maintenance, offering a potential strategy to improve GBM treatment.Methods: Single-cell RNA-seq was used to assess SUV39H2 expression in GSCs. GSC growth and stemness were evaluated using tumorsphere formation assay and extreme limiting dilution assay. Gene expression at the mRNA and protein levels was measured by RT-qPCR and western blot, respectively. Publicly available datasets were analyzed to investigate SUV39H2 expression patterns and its clinical prognostic significance in GBM and glioma.Results: SUV39H2 is overexpressed in GSCs relative to non-stem GBM cells. Its depletion impairs GSC proliferation and stemness. Co-targeting SUV39H2 and SUV39H1 enhances GSC disruption. High SUV39H2 expression correlates with poor glioma prognosis.Conclusion: SUV39H2 is a novel regulator of GSC maintenance. Dual targeting of SUV39H2 and SUV39H1 May offer a potential therapeutic approach for GBM.","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"1225-1232"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12674267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DNA methylation age acceleration mediates the relationship between systemic inflammation and cognitive impairment. DNA甲基化年龄加速介导全身性炎症和认知障碍之间的关系。

IF 2.6 4区医学

Epigenomics Pub Date : 2025-12-01 Epub Date: 2025-12-08 DOI: 10.1080/17501911.2025.2595905

César Higgins Tejera, Peiyao Zhu, Erin B Ware, Margaret T Hicken, Matthew Zawistowski, Lindsay C Kobayashi, Dominika Seblova, Jennifer Manly, Bhramar Mukherjee, Kelly M Bakulski

{"title":"DNA methylation age acceleration mediates the relationship between systemic inflammation and cognitive impairment.","authors":"César Higgins Tejera, Peiyao Zhu, Erin B Ware, Margaret T Hicken, Matthew Zawistowski, Lindsay C Kobayashi, Dominika Seblova, Jennifer Manly, Bhramar Mukherjee, Kelly M Bakulski","doi":"10.1080/17501911.2025.2595905","DOIUrl":"10.1080/17501911.2025.2595905","url":null,"abstract":"Background: Chronic inflammation and DNA methylation are potential mechanisms in dementia etiology. The linkage between inflammation and DNA methylation age acceleration in shaping dementia risk remains understudied. We explored the association of inflammatory cytokines with cognitive impairment and whether DNA methylation age acceleration mediates this relationship.Research design and methods: Using data from the 2016 Health and Retirement Study (n = 3,346, age >50), we estimate the associations between each inflammatory cytokine (interleukin-6 (IL-6), C-reactive protein (CRP), and insulin-like growth factor-1 (IGF-1)), and cognitive status, classified using the Langa-Weir method. We tested if DNA methylation age acceleration mediated the relationship between systemic inflammation and cognitive impairment, adjusting for sociodemographic, behavioral factors, chronic conditions, and cell-type proportions.Results: Cognitive impairment prevalence was 16%. A doubling of IL-6 was associated with a 12% higher odds of cognitive impairment (OR = 1.12, 95% CI: 1.02-1.22), and 0.77 years of GrimAge acceleration (95% CI: 0.64-0.90). Similar associations were found for CRP and IGF-1. Mediation analysis indicated that 17.7% (95% CI: 7.0-50.9%) of the IL-6-cognitive impairment association was mediated by the GrimAge acceleration. Comparable mediated estimates were found for CRP and IGF-1.Conclusions: Systemic inflammation is associated with cognitive impairment, with suggestive evidence that this relationship is partially mediated through DNA methylation age acceleration.","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"1399-1409"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145700081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Periconceptional and prenatal nutrition shapes the fetal epigenomic landscape. 围孕期和产前营养塑造胎儿表观基因组景观。

IF 2.6 4区医学

Epigenomics Pub Date : 2025-12-01 Epub Date: 2025-12-28 DOI: 10.1080/17501911.2025.2605942

Mariana Parenti, Alison G Paquette

{"title":"Periconceptional and prenatal nutrition shapes the fetal epigenomic landscape.","authors":"Mariana Parenti, Alison G Paquette","doi":"10.1080/17501911.2025.2605942","DOIUrl":"10.1080/17501911.2025.2605942","url":null,"abstract":"Nutrition during pregnancy can influence fetal development and health across the lifespan. Prenatal nutrition is mechanistically linked to the epigenetic landscape because nutrients supply methyl groups and regulate microRNAs and proteins involved in epigenetic modifications. This review focuses on the epigenomic landscape in both the umbilical cord blood, as a window into fetal development, and in the placenta, as the master regulator of fetal nutrition. We highlight associations between the epigenome and nutrients found in prenatal multiple micronutrient supplements, including one carbon metabolism nutrients, antioxidant vitamins, vitamin D, trace minerals, and omega-3 polyunsaturated fatty acids. We discuss challenges in this field including reliance on observational studies, non-linear relationships, cell type-specific effects, and sex-specific effects. We also highlight emerging approaches to explore the role of nutritional epigenomics in development including critical windows of exposure and novel epigenetic and epitranscriptomic features by applying new technological advancements. A better understanding of how nutrients affect the epigenomic landscape in early life can inform further mechanistic studies and improve clinical guidance surrounding nutrient and intake during pregnancy, ultimately leading to improved maternal and fetal outcomes and health throughout the lifespan.","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"1621-1639"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Defect of MLH1 expression sensitized esophageal squamous cell carcinoma cells to Polθ inhibitor. MLH1表达缺陷导致食管鳞癌细胞对Polθ抑制剂敏感。

IF 2.6 4区医学

Epigenomics Pub Date : 2025-12-01 Epub Date: 2025-10-30 DOI: 10.1080/17501911.2025.2579975

Bo Zhou, Meiying Zhang, Cheng Zhu, Aiai Gao, Xiaomo Su, Mingzhou Guo

{"title":"Defect of MLH1 expression sensitized esophageal squamous cell carcinoma cells to Polθ inhibitor.","authors":"Bo Zhou, Meiying Zhang, Cheng Zhu, Aiai Gao, Xiaomo Su, Mingzhou Guo","doi":"10.1080/17501911.2025.2579975","DOIUrl":"10.1080/17501911.2025.2579975","url":null,"abstract":"Background: A large scale detection of MLH1 methylation is lacking in esophageal cancer. MLH1 is a well-known mismatch repair gene. The mechanism of MLH1 in DNA double strand break (DSB) repair remains unclear.Methods: Esophageal cancer cell lines and 1018 cases of primary cancer samples were employed. Methylation specific PCR, Western Blot, and CRISPR/Cas9 knockout technique were utilized.Results: Methylation of MLH1 was detected in 3.93%. MLH1 methylation was significantly associated with tumor differentiation, male gender, smoking, and tumor size (all p < 0.05). The median overall survival (OS) was 24.7 months (95% CI 13.4-36.0) and 51.5 months (95% CI 40.4-62.5) in MLH1 methylated and unmethylated groups, respectively. OS was shorter in MLH1 methylated compared to unmethylated group patients (p < 0.01). Multivariate factor analysis indicated that MLH1 methylation is an independent poor prognosis marker (p < 0.05). MLH1 promotes ataxia telangiectasia mutated (ATM), ataxia telangiectasia and RAD3-related (ATR), and non-homologous end-joining repair (NHEJ), while inhibiting microhomology-mediated end joining (MMEJ) repair signaling pathways. Deletion of MLH1 sensitized esophageal cancer cells to novobiocin.Conclusions: MLH1 plays important roles in DSB repair and deletion of MLH1 sensitizes ESCC cells to Polθ inhibitor.","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"1347-1354"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0