Epigenetics最新文献_第2页

Placental malaria induces a unique methylation profile associated with fetal growth restriction. 胎盘疟疾诱导与胎儿生长限制相关的独特甲基化谱。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-03-06 DOI: 10.1080/15592294.2025.2475276

Nida Ozarslan, Corina Mong, John Ategeka, Lin Li, Sirirak Buarpung, Joshua F Robinson, Jimmy Kizza, Abel Kakuru, Moses R Kamya, Grant Dorsey, Philip J Rosenthal, Stephanie L Gaw

{"title":"Placental malaria induces a unique methylation profile associated with fetal growth restriction.","authors":"Nida Ozarslan, Corina Mong, John Ategeka, Lin Li, Sirirak Buarpung, Joshua F Robinson, Jimmy Kizza, Abel Kakuru, Moses R Kamya, Grant Dorsey, Philip J Rosenthal, Stephanie L Gaw","doi":"10.1080/15592294.2025.2475276","DOIUrl":"10.1080/15592294.2025.2475276","url":null,"abstract":"Fetal growth restriction (FGR) is associated with perinatal death and adverse birth outcomes, as well as long-term complications, including increased childhood morbidity, abnormal neurodevelopment, and cardio-metabolic diseases in adulthood. Placental epigenetic reprogramming associated with FGR may mediate these long-term outcomes. Placental malaria (PM), characterized by sequestration of Plasmodium falciparum-infected erythrocytes in placental intervillous space, is the leading global cause of FGR, but its impact on placental epigenetics is unknown. We hypothesized that placental methylomic profiling would reveal common and distinct mechanistic pathways of non-malarial and PM-associated FGR. We analyzed placentas from a US cohort with no malaria exposure (n = 12) and a cohort from eastern Uganda, a region with a high prevalence of malaria (n = 12). From each site, 8 cases of FGR and 4 healthy controls were analyzed. PM was diagnosed by placental histopathology. We compared the methylation levels of over 850K CpGs of the placentas using Infinium MethylationEPIC v1 microarray. Non-malarial FGR was associated with 65 differentially methylated CpGs (DMCs), whereas PM-FGR was associated with 133 DMCs, compared to their corresponding controls without FGR. One DMC (cg16389901, located in the promoter region of BMP4) was commonly hypomethylated in both groups. We identified 522 DMCs between non-malarial FGR vs. PM-FGR placentas, independent of differing geographic location or cellular composition. Placentas with PM-associated FGR have distinct methylation profiles compared to placentas with non-malarial FGR, suggesting novel epigenetic reprogramming in response to malaria. Larger cohort studies are needed to determine the distinct long-term health outcomes in PM-associated FGR pregnancies.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2475276"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572486","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}

引用次数: 0

SIRT1/DNMT3B-mediated epigenetic gene silencing in response to phytoestrogens in mammary epithelial cells. SIRT1/ dnmt3b介导的表观遗传基因沉默对乳腺上皮细胞植物雌激素的响应

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-03-03 DOI: 10.1080/15592294.2025.2473770

Yuexi Ma, Cayla Boycott, Jiaxi Zhang, Rekha Gomilar, Tony Yang, Barbara Stefanska

{"title":"SIRT1/DNMT3B-mediated epigenetic gene silencing in response to phytoestrogens in mammary epithelial cells.","authors":"Yuexi Ma, Cayla Boycott, Jiaxi Zhang, Rekha Gomilar, Tony Yang, Barbara Stefanska","doi":"10.1080/15592294.2025.2473770","DOIUrl":"10.1080/15592294.2025.2473770","url":null,"abstract":"We performed an integrated analysis of genome-wide DNA methylation and expression datasets in normal cells and healthy animals exposed to polyphenols with estrogenic activity (i.e. phytoestrogens). We identified that phytoestrogens target genes linked to disrupted cellular homeostasis, e.g. genes limiting DNA break repair (RNF169) or promoting ribosomal biogenesis (rDNA). Existing evidence suggests that DNA methylation may be governed by sirtuin 1 (SIRT1) deacetylase via interactions with DNA methylating enzymes, specifically DNMT3B. Since SIRT1 was reported to be regulated by phytoestrogens, we test whether phytoestrogens suppress genes related to disrupted homeostasis via SIRT1/DNMT3B-mediated transcriptional silencing. Human MCF10A mammary epithelial cells were treated with phytoestrogens, pterostilbene (PTS) or genistein (GEN), followed by analysis of cell growth, DNA methylation, gene expression, and SIRT1/DNMT3B binding. SIRT1 occupancy at the selected phytoestrogen-target genes, RNF169 and rDNA, was accompanied by consistent promoter hypermethylation and gene downregulation in response to GEN, but not PTS. GEN-mediated hypermethylation and SIRT1 binding were linked to a robust DNMT3B enrichment at RNF169 and rDNA promoters. This was not observed in cells exposed to PTS, suggesting a distinct mechanism of action. Although both SIRT1 and DNMT3B bind to RNF169 and rDNA promoters upon GEN, the two proteins do not co-occupy the regions. Depletion of SIRT1 abolishes GEN-mediated decrease in rDNA expression, suggesting SIRT1-dependent epigenetic suppression of rDNA by GEN. These findings enhance our understanding of the role of SIRT1-DNMT3B interplay in epigenetic mechanisms mediating the impact of phytoestrogens on cell biology and cellular homeostasis.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2473770"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540624","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}

引用次数: 0

DNA methylation markers of insulin resistance surrogate measures in the Atherosclerosis Risk in Communities (ARIC) study. 社区动脉粥样硬化风险（ARIC）研究中胰岛素抵抗的DNA甲基化标志物替代措施

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-05-06 DOI: 10.1080/15592294.2025.2498857

Jeewoen Shin, Jan Bressler, Megan L Grove, Michael Brown, Elizabeth Selvin, James S Pankow, Myriam Fornage, Alanna C Morrison, Chloé Sarnowski

{"title":"DNA methylation markers of insulin resistance surrogate measures in the Atherosclerosis Risk in Communities (ARIC) study.","authors":"Jeewoen Shin, Jan Bressler, Megan L Grove, Michael Brown, Elizabeth Selvin, James S Pankow, Myriam Fornage, Alanna C Morrison, Chloé Sarnowski","doi":"10.1080/15592294.2025.2498857","DOIUrl":"https://doi.org/10.1080/15592294.2025.2498857","url":null,"abstract":"Insulin resistance (IR) is a risk factor for cardiovascular diseases and type 2 diabetes. Associations between DNA methylation (DNAm) and IR have been less studied in African ancestry (AA) populations than those of European ancestry (EA). We aimed to identify associations between whole blood DNAm and IR in up to 1,811 AA and 964 EA participants from the Atherosclerosis Risk in Communities (ARIC) study. We quantified IR using three surrogate measures: the homeostasis model assessment of insulin resistance (HOMA-IR), the triglyceride-glucose index (TyG), and the triglyceride glucose-body mass index (TyG-BMI). We used ancestry-stratified linear regression models to conduct epigenome-wide association studies of IR, adjusting for batch effects and relevant covariates. Among 484,436 tested CpG sites, 39 were significantly associated with IR, of which 31% (10 in AA and two in EA) were associated with TyG-BMI and not previously reported for IR or related traits. These include a positive association at cg18335991-SEMA7A in AA. SEMA7A inhibits adipogenesis of preadipocytes and lipogenesis of mature adipocytes. DNAm levels at cg18335991 have been reported to be negatively associated with SEMA7A expression in blood. After additionally adjusting for smoking and drinking status, 15 of the 39 significant CpG sites remained significant or suggestive. Our study identified novel IR-associated CpG sites, contributing to a broader understanding of the epigenetic mechanisms underlying IR in diverse populations.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2498857"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970825","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}

引用次数: 0

Higher sperm H3K4me3 levels are associated with idiopathic recurrent pregnancy loss. 较高的精子H3K4me3水平与特发性复发性妊娠丢失有关。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-04-29 DOI: 10.1080/15592294.2025.2498859

Delna Irani, Deepshikha Arya, Deepti Tandon, Vandana Bansal, Anushree Patil, Dipty Singh

{"title":"Higher sperm H3K4me3 levels are associated with idiopathic recurrent pregnancy loss.","authors":"Delna Irani, Deepshikha Arya, Deepti Tandon, Vandana Bansal, Anushree Patil, Dipty Singh","doi":"10.1080/15592294.2025.2498859","DOIUrl":"https://doi.org/10.1080/15592294.2025.2498859","url":null,"abstract":"During fertilization, spermatozoa contribute genetic and epigenetic factors such as chromatin packaged with protamines and histones; DNA methylome, non-coding RNAs, etc. Human sperm chromatin retains 5-15% nucleosomes which can play a key role in embryonic development. Recurrent pregnancy loss (RPL) is a condition mainly attributed to defects in embryo and placenta development. Majority of the known RPL factors are of maternal contribution, while ~50% RPL cases are termed idiopathic (iRPL). In addition to paternal genetic factors, epigenetic factors via sperm could also be responsible for iRPL. Hence, we investigated alterations in retained nucleosome content of iRPL sperm (n = 46) as compared to fertile male population (n = 40). We measured the relative abundance of core histone H4 and Protamine-2 content along with the modified histones H4Ac, H3K4me3, H3K27me3 and H3K9me3 by flow cytometry. H4 and Protamine-2 levels were comparable in both groups and showed significant negative correlation. The iRPL group had significantly higher levels of sperm H3K4me3 as compared to the fertile control group. The other modified histones and protamine levels showed no significant alterations. Furthermore, sperm DFI was found to be significantly positively correlated with H4 levels in both groups. No significant correlation was observed between sperm 5-mC levels with H4 and other modified histone levels. A fraction of H3K4me3 enrichment is now known to resist embryonic epigenetic reprogramming; and hence, such elevated levels in the sperm would question its developmental competence leading to RPL pathology. Also, incidence of sperm DNA fragmentation is associated with increased histone retention in both fertile and iRPL cases.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2498859"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984748","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}

引用次数: 0

Glucocorticoid receptor epigenetic activity in the heart. 心脏中糖皮质激素受体的表观遗传活性。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-02-25 DOI: 10.1080/15592294.2025.2468113

Olukunle Akinborewa, Mattia Quattrocelli

{"title":"Glucocorticoid receptor epigenetic activity in the heart.","authors":"Olukunle Akinborewa, Mattia Quattrocelli","doi":"10.1080/15592294.2025.2468113","DOIUrl":"10.1080/15592294.2025.2468113","url":null,"abstract":"The glucocorticoid receptor (GR) is a critical nuclear receptor that regulates gene expression in diverse tissues, including the heart, where it plays a key role in maintaining cardiovascular health. GR signaling influences essential processes within cardiomyocytes, including hypertrophy, calcium handling, and metabolic balance, all of which are vital for proper cardiac function. Dysregulation of GR activity has been implicated in various cardiovascular diseases (CVDs), highlighting the potential of GR as a therapeutic target. Remarkably, recent insights into GR's epigenetic regulation and its interaction with circadian rhythms reveal opportunities to optimize therapeutic strategies by aligning glucocorticoid administration with circadian timing. In this review, we provide an overview of the glucocorticoid receptor's role in cardiac physiology, detailing its genomic and non-genomic pathways, interactions with epigenetic and circadian regulatory mechanisms, and implications for cardiovascular disease. By dissecting these molecular interactions, this review outlines the potential of epigenetically informed and circadian-timed interventions that could change the current paradigms of CVD treatments in favor of precise and effective therapies.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2468113"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499980","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}

引用次数: 0

DNA-based cell typing in menstrual effluent identifies cell type variation by sample collection method: toward noninvasive biomarker development for women's health. 基于dna的月经流出液细胞分型通过样本收集方法识别细胞类型变化：面向女性健康的无创生物标志物开发。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-01-18 DOI: 10.1080/15592294.2025.2453275

Irma M Vlasac, Hannah G Stolrow, Zaneta M Thayer, Brock C Christensen, Luisa Rivera

引用次数: 0

Chromatin accessibility profiling of Treg cells in acute urticaria. 急性荨麻疹Treg细胞的染色质可及性分析。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-05-12 DOI: 10.1080/15592294.2025.2503126

Leilei Wen, Xiaojing Zhang, Qiaoshan Yang, Fusheng Zhou

{"title":"Chromatin accessibility profiling of Treg cells in acute urticaria.","authors":"Leilei Wen, Xiaojing Zhang, Qiaoshan Yang, Fusheng Zhou","doi":"10.1080/15592294.2025.2503126","DOIUrl":"10.1080/15592294.2025.2503126","url":null,"abstract":"Acute urticaria can be a presenting symptom of anaphylaxis characterized by transient red swellings or fulminant wheals, often accompanied by severe pruritus. Numerous studies have substantiated the important involvement of regulatory T cells (Tregs) in the occurrence of allergic diseases and autoimmune diseases. However, the role of Tregs in the pathogenesis of acute urticaria is unclear. In this study, we found that the frequency of Tregs in peripheral blood mononuclear cells (PBMCs) was decreased in patients with acute urticaria compared with normal controls by flow cytometry. Analysis of Assay for transposase-accessible chromatin with sequencing (ATAC-seq) data identified 28 differentially accessible regions comparing Tregs from healthy individuals and patients with acute urticaria, all showing increased chromatin accessibility in the Tregs from acute urticaria. IL-1b was highly expressed in sera of patients with acute urticaria and the level of IL-1b was moderately positively related to white blood cell count. The elevated expression of IL-1b may be due to the diminished immune-suppressive function following the decline of Tregs in this study. We found that IL1B gene expression was also significantly increased in the skin lesions of both chronic spontaneous urticaria and solar urticaria compared to healthy controls. IL1B might play a key role in the development of acute urticaria and IL1B could be a potential prognostic biomarker and therapeutic target in urticaria.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2503126"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978049","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}

引用次数: 0

Research progress on the mechanism of tumor cell ferroptosis regulation by epigenetics. 肿瘤细胞铁下垂调控机制的表观遗传学研究进展。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-05-06 DOI: 10.1080/15592294.2025.2500949

Yuyang Xiao, Mengyang He, Xupeng Zhang, Meng Yang, Zhangchi Yuan, Shanhu Yao, Yuexiang Qin

{"title":"Research progress on the mechanism of tumor cell ferroptosis regulation by epigenetics.","authors":"Yuyang Xiao, Mengyang He, Xupeng Zhang, Meng Yang, Zhangchi Yuan, Shanhu Yao, Yuexiang Qin","doi":"10.1080/15592294.2025.2500949","DOIUrl":"https://doi.org/10.1080/15592294.2025.2500949","url":null,"abstract":"Cancer remains a significant barrier to human longevity and a leading cause of mortality worldwide. Despite advancements in cancer therapies, challenges such as cellular toxicity and drug resistance to chemotherapy persist. Regulated cell death (RCD), once regarded as a passive process, is now recognized as a programmed mechanism with distinct biochemical and morphological characteristics, thereby presenting new therapeutic opportunities. Ferroptosis, a novel form of RCD characterized by iron-dependent lipid peroxidation and unique mitochondrial damage, differs from apoptosis, autophagy, and necroptosis. It is driven by reactive oxygen species (ROS)-induced lipid peroxidation and is implicated in tumorigenesis, anti-tumor immunity, and resistance, particularly in tumors undergoing epithelial-mesenchymal transition. Moreover, ferroptosis is associated with ischemic organ damage, degenerative diseases, and aging, regulated by various cellular metabolic processes, including redox balance, iron metabolism, and amino acid, lipid, and glucose metabolism. This review focuses on the role of epigenetic factors in tumor ferroptosis, exploring their mechanisms and potential applications in cancer therapy. It synthesizes current knowledge to provide a comprehensive understanding of epigenetic regulation in tumor cell ferroptosis, offering insights for future research and clinical applications.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2500949"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959332","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}

引用次数: 0

Differential methylation in blood pressure control genes is associated to essential hypertension in African Brazilian populations. 在非裔巴西人群中，血压控制基因的差异甲基化与原发性高血压有关。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-03-27 DOI: 10.1080/15592294.2025.2477850

Camila Cristina Avila Martins, Mariana Maschietto, Lilian Kimura, Lucas Alvizi, Kelly Nunes, Vinícius Magalhães Borges, Ana Cristina Victorino Krepischi, Regina Célia Mingroni-Netto

{"title":"Differential methylation in blood pressure control genes is associated to essential hypertension in African Brazilian populations.","authors":"Camila Cristina Avila Martins, Mariana Maschietto, Lilian Kimura, Lucas Alvizi, Kelly Nunes, Vinícius Magalhães Borges, Ana Cristina Victorino Krepischi, Regina Célia Mingroni-Netto","doi":"10.1080/15592294.2025.2477850","DOIUrl":"10.1080/15592294.2025.2477850","url":null,"abstract":"While genetic studies have provided insights into essential hypertension (EH, defined by high blood pressure ≥140/90 mmHg), investigation through epigenetics may address gaps in understanding its heritability. This study focused on African Brazilian populations in Vale do Ribeira River region, due to their high hypertension prevalence. We aimed to determine if DNA methylation is linked to hypertension susceptibility, through a genome-wide evaluation of 80 peripheral blood samples from normotensive (39) and hypertensive (41) individuals, with Infinium Methylation EPIC BeadChip platform. Data were analyzed using ChAMP package and cross-referenced with information from databases such as EWAS Atlas, GWAS catalog, GeneCards, literature, and tools such as VarElect and EWAS Toolkit. The comparison between hypertensive and normotensive revealed 190 differentially methylated CpG positions (DMPs) and 46 differentially methylated regions (DMRs), both with p-value ≤0.05. Among the DMPs, 27 were found to have a plausible role in blood pressure. Among the DMRs, those mapped to ABAT, BLCAP, CERS3, EIF4E, FMN1, GABBR1, HLA-DQB2, HOXA5, IL5RA, KCNH2, MIR487B, MIR539, MIR886, MKRN3, NUDT12, PON3, RNF39, RWDD3, and TSHBS1 were highlighted because of their lowest p-values, current literature, and/or VarElect prioritization. Our findings suggest that differences in methylation contribute to the high susceptibility to essential hypertension in these populations.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2477850"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718218","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}

引用次数: 0

METTL14-mediated m⁶A modification of DDIT4 promotes its mRNA stability in aging-related idiopathic pulmonary fibrosis. mettl14介导的m6A修饰DDIT4促进其mRNA在衰老相关特发性肺纤维化中的稳定性。

IF 2.9 3区生物学

Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-02-07 DOI: 10.1080/15592294.2025.2462898

Dan Li, Li Qian, Yufeng Du, Lifang Liu, Ziyue Sun, Yongkang Han, Xiangrui Guo, Chao Shen, Zheng Zhang, Xuejun Liu

{"title":"METTL14-mediated m6A modification of DDIT4 promotes its mRNA stability in aging-related idiopathic pulmonary fibrosis.","authors":"Dan Li, Li Qian, Yufeng Du, Lifang Liu, Ziyue Sun, Yongkang Han, Xiangrui Guo, Chao Shen, Zheng Zhang, Xuejun Liu","doi":"10.1080/15592294.2025.2462898","DOIUrl":"10.1080/15592294.2025.2462898","url":null,"abstract":"Although N6-methyladenosine (m6A) may be related to the pathogenesis of fibrotic process, the mechanism of m6A modification in aging-related idiopathic pulmonary fibrosis (IPF) remains unclear. Three-milliliter venous blood was collected from IPF patients and healthy controls. MeRIP-seq and RNA-seq were utilized to investigate differential m6A modification. The expressions of identified m6A regulator and target gene were validated using MeRIP-qPCR and real-time PCR. Moreover, we established an animal model and a senescent model of A549 cells to explore the associated molecular mechanism. Our study provided a panorama of m6A methylation in IPF. Increased peaks (3756) and decreased peaks (4712) were observed in the IPF group. The association analysis showed that 749 DEGs were affected by m6A methylation in IPF. Among the m6A regulators, the expression of METTL14 decreased in IPF. The m6A level of our interested gene DDIT4 decreased significantly, but the mRNA level of DDIT4 was higher in IPF. This was further verified in bleomycin-induced pulmonary fibrosis. At the cellular level, it was further confirmed that METTL14 and DDIT4 might participate in the senescence of alveolar epithelial cells. The downregulation of METTL14 might inhibit the decay of DDIT4 mRNA by reducing the m6A modification level of DDIT4 mRNA, leading to high expression of DDIT4 mRNA and protein. Our study provided a panorama of m6A alterations in IPF and discovered METTL14 as a potential intervention target for epigenetic modification in IPF. These results pave the way for future investigations regarding m6A modifications in aging-related IPF.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2462898"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364170","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}

引用次数: 0