Clinical Epigenetics最新文献

{"title":"miR-182 promoter hypermethylation predicts the better outcome of AML patients treated with AZA + VEN in a real-world setting.","authors":"Yilan Xu, Danyang Li, Na Wang, Bei Ge, Chen Meng, Min Zhao, Zihan Lin, Min Li, Yigang Yuan, Yue Cai, Liuzhi Shi, Shenmeng Gao, Haige Ye","doi":"10.1186/s13148-025-01823-1","DOIUrl":"https://doi.org/10.1186/s13148-025-01823-1","url":null,"abstract":"<p><strong>Background: </strong>5-Azacytidine (AZA) combined with the BCL2 inhibitor Venetoclax (VEN) is the standard treatment for elderly acute myeloid leukemia (AML) patients or those who are unfit for intensive chemotherapy (elderly or unfit AML). However, an effective and rapid predictive biomarker to predict treatment outcome remains elusive.</p><p><strong>Methods: </strong>miR-182 promoter methylation was measured in 94 AZA + VEN-treated elderly or unfit AML patients and 20 normal controls (NCs) samples. To determine whether miR-182 promoter methylation is a predictive marker of clinical outcomes in AZA + VEN-treated AML patients in a real-world setting, we analyzed and compared the complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate, overall survival (OS), and leukemia free-survival (LFS) across different methylation groups: miR-182 promoter hypomethylation (median value < 20.21%) and hypermethylation (> 20.21%) in a retrospective study.</p><p><strong>Results: </strong>The average methylation frequency was markedly higher in 94 AZA + VEN-treated elderly or unfit AML patients than that in 20 NCs. However, some AML patients (11.7%) still presented low miR-182 promoter methylation (< 10%). The average time to obtain CR/CRi was shorter in AML patients with miR-182 promoter hypermethylation than AML with hypomethylation. Moreover, the median OS and LFS were longer in AML patients with miR-182 promoter hypermethylation than AML with hypomethylation. Finally, the area under the curve (AUC) for 1-year mortality was 0.831, for 2-year was 0.788, and for 3-year was 0.800.</p><p><strong>Conclusions: </strong>AML patients with miR-182 promoter hypermethylation have better outcomes. miR-182 promoter methylation is a predictive biomarker for AZA + VEN-treated AML patients.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"18"},"PeriodicalIF":4.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related changes in DNA methylation in a sample of elderly Brazilians.","authors":"Hayley Welsh, Caio M P F Batalha, Weili Li, Nadja C Souza-Pinto, Yeda A O Duarte, Michel S Naslavsky, Esteban J Parra","doi":"10.1186/s13148-025-01821-3","DOIUrl":"https://doi.org/10.1186/s13148-025-01821-3","url":null,"abstract":"<p><strong>Background: </strong>Age-related changes in DNA methylation (DNAm) play a critical role in regulating gene expression. However, most epigenome-wide association studies have predominantly focused on individuals of European descent. This study aims to characterize longitudinal changes in DNAm patterns in a cohort of elderly Brazilian participants.</p><p><strong>Methods: </strong>DNAm profiles were collected approximately nine years apart from 23 elderly Brazilian individuals using the Illumina Infinium MethyationEPIC BeadChip. Using mixed-effects models, we examined changes in DNAm patterns using both quantitative age and binary timepoint (e.g., baseline vs. follow-up) as predictors of interest to identify differentially methylated positions (DMPs). Significant DMPs were compared with a list of previously identified age-related DMPs. Differentially methylated regions (DMRs) were also identified using DMRcate. Gene ontology (GO) pathway enrichment analyses were performed to explore the functional significance of identified DMPs and DMRs.</p><p><strong>Results: </strong>Of the 586,229 autosomal probes included in the differential methylation analyses, 2768 significant (FDR < 0.05) age-associated DMPs (aDMPs) and 2757 significant (FDR < 0.05) timepoint-associated DMPs (tpDMPs) were identified. Of the 2768 aDMPs, 1471 were replicated from previous studies. Of the 1297 non-replicated CpGs, 77.4% were exclusive to the EPIC array. The DMR analyses identified 305 age-associated DMRs (aDMRs) and 372 timepoint-associated DMRs (tpDMRs). Both aDMPs and aDMRs exhibited age-related hypermethylation within CpG islands and promoter regions of the genome, whereas hypomethylation predominantly occurred in interCGI and intergenic regions and introns. The GO enrichment analyses identified several neurological and cognition-related pathways enriched for hypermethylated CpG islands, many of which were mapped near transcription start sites and first exon regions.</p><p><strong>Conclusions: </strong>This longitudinal study identified age-associated and timepoint-associated DMPs and DMRs in a sample of elderly Brazilians. Most of the non-replicated CpGs were found to be on the new EPIC array, suggesting that more age-related studies using the EPIC array are required to validate these CpGs. The GO pathway enrichment analyses identified age-related enrichment of several gene sets related to cognitive and physical decline in elderly populations. The enrichment of these sites could provide evidence for age-related neurodegeneration and cognitive decline in elderly populations.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"17"},"PeriodicalIF":4.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validating a clinically based MS-MLPA threshold through comparison with Sanger sequencing in glioblastoma patients.","authors":"Halka Lhotska, Karolina Janeckova, Hana Cechova, Jaromir Macoun, Tatiana Aghova, Libuse Lizcova, Karla Svobodova, Lucie Hodanova, Dora Konecna, Jiri Soukup, Filip Kramar, David Netuka, Zuzana Zemanova","doi":"10.1186/s13148-025-01822-2","DOIUrl":"https://doi.org/10.1186/s13148-025-01822-2","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma is the commonest malignant brain tumor and has a very poor prognosis. Reduced expression of the MGMT gene (10q26.3), influenced primarily by the methylation of two differentially methylated regions (DMR1 and DMR2), is associated with a good response to temozolomide treatment. However, suitable methods for detecting the methylation of the MGMT gene promoter and setting appropriate cutoff values are debated.</p><p><strong>Results: </strong>A cohort of 108 patients with histologically and genetically defined glioblastoma was retrospectively examined with methylation-specific Sanger sequencing (sSeq) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) methods. The DMR2 region was methylated in 29% of samples, whereas DMR1 was methylated in 12% of samples. Methylation detected with the MS-MLPA method using probes MGMT_215, MGMT_190, and MGMT_124 from the ME012-A1 kit (located in DMR1 and DMR2) correlated with the methylation of the corresponding CpG dinucleotides detected with sSeq (p = 0.005 for probe MGMT_215; p < 0.001 for probe MGMT_190; p = 0.016 for probe MGMT_124). The threshold for methylation detection with the MS-MLPA method was calculated with a ROC curve analysis and principal components analysis of the data obtained with the MS-MLPA and sSeq methods, yielding a weighted value of 0.362. Thus, methylation of the MGMT gene promoter was confirmed in 36% of samples. These patients had statistically significantly better overall survival (p = 0.003).</p><p><strong>Conclusions: </strong>Our results show that the threshold for methylation detection with the MS-MLPA method determined here is useful from a diagnostic perspective because it allows the stratification of patients who will benefit from specific treatment protocols, including temozolomide. Detailed analysis of the MGMT gene promoter enables the more-precise and personalized treatment of patients with glioblastoma.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"16"},"PeriodicalIF":4.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of myocardial energy metabolism perturbations in diabetic cardiomyopathy: from the perspective of novel protein post-translational modifications.","authors":"Dongze Li, Li Zhang, Qiming Gong, Huilan Deng, Changfang Luo, Tingting Zhou, Wei Huang, Yong Xu","doi":"10.1186/s13148-025-01814-2","DOIUrl":"10.1186/s13148-025-01814-2","url":null,"abstract":"<p><p>Diabetic cardiomyopathy (DbCM), a significant chronic complication of diabetes, manifests as myocardial hypertrophy, fibrosis, and other pathological alterations that substantially impact cardiac function and elevate the risk of cardiovascular diseases and patient mortality. Myocardial energy metabolism disturbances in DbCM, encompassing glucose, fatty acid, ketone body and lactate metabolism, are crucial factors that contribute to the progression of DbCM. In recent years, novel protein post-translational modifications (PTMs) such as lactylation, β-hydroxybutyrylation, and succinylation have been demonstrated to be intimately associated with the myocardial energy metabolism process, and in conjunction with acetylation, they participate in the regulation of protein activity and gene expression activity in cardiomyocytes. This review examines the epigenetic pathogenesis of DbCM, primarily focusing on myocardial energy metabolism perturbations and novel PTMs associated with them. It provides a detailed analysis of the mechanisms of these novel PTMs in DbCM to enhance the understanding of DbCM pathophysiology and establish a theoretical foundation for the development of new treatment strategies for DbCM.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"15"},"PeriodicalIF":4.8,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood-based epigenome-wide association study and prediction of alcohol consumption.","authors":"Elena Bernabeu, Aleksandra D Chybowska, Jacob K Kresovich, Matthew Suderman, Daniel L McCartney, Robert F Hillary, Janie Corley, Maria Del C Valdés-Hernández, Susana Muñoz Maniega, Mark E Bastin, Joanna M Wardlaw, Zongli Xu, Dale P Sandler, Archie Campbell, Sarah E Harris, Andrew M McIntosh, Jack A Taylor, Paul Yousefi, Simon R Cox, Kathryn L Evans, Matthew R Robinson, Catalina A Vallejos, Riccardo E Marioni","doi":"10.1186/s13148-025-01818-y","DOIUrl":"10.1186/s13148-025-01818-y","url":null,"abstract":"<p><p>Alcohol consumption is an important risk factor for multiple diseases. It is typically assessed via self-report, which is open to measurement error through recall bias. Instead, molecular data such as blood-based DNA methylation (DNAm) could be used to derive a more objective measure of alcohol consumption by incorporating information from cytosine-phosphate-guanine (CpG) sites known to be linked to the trait. Here, we explore the epigenetic architecture of self-reported weekly units of alcohol consumption in the Generation Scotland study. We first create a blood-based epigenetic score (EpiScore) of alcohol consumption using elastic net penalized linear regression. We explore the effect of pre-filtering for CpG features ahead of elastic net, as well as differential patterns by sex and by units consumed in the last week relative to an average week. The final EpiScore was trained on 16,717 individuals and tested in four external cohorts: the Lothian Birth Cohorts (LBC) of 1921 and 1936, the Sister Study, and the Avon Longitudinal Study of Parents and Children (total N across studies > 10,000). The maximum Pearson correlation between the EpiScore and self-reported alcohol consumption within cohort ranged from 0.41 to 0.53. In LBC1936, higher EpiScore levels had significant associations with poorer global brain imaging metrics, whereas self-reported alcohol consumption did not. Finally, we identified two novel CpG loci via a Bayesian penalized regression epigenome-wide association study of alcohol consumption. Together, these findings show how DNAm can objectively characterize patterns of alcohol consumption that associate with brain health, unlike self-reported estimates.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"14"},"PeriodicalIF":4.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship between enriched environment and neurodegeneration: a review from mechanism to therapy.","authors":"Yuan-Qiao Xu, Yanjiao Chen, Jia-Xin Xing, Jun Yao","doi":"10.1186/s13148-025-01820-4","DOIUrl":"10.1186/s13148-025-01820-4","url":null,"abstract":"<p><p>Enriched environment (EE), as a non-pharmacological intervention, has garnered considerable attention for its potential to ameliorate neurodegenerative diseases (NDs). This review delineated the impact of EE on the biological functions associated with NDs, emphasizing its role in enhancing neural plasticity, reducing inflammation, and bolstering cognitive performance. We discussed the molecular underpinnings of the effects of EE, including modulation of key signaling pathways such as extracellular regulated kinase 1/2 (ERK1/2), mitogen-activated protein kinases (MAPK), and AMPK/SIRT1, which were implicated in neuroprotection and synaptic plasticity. Additionally, we scrutinized the influence of EE on epigenetic modifications and autophagy, processes pivotal to ND pathogenesis. Animal models, encompassing both rodents and larger animals, offer insights into the disease-modifying effects of EE, underscoring its potential as a complementary approach to pharmacological interventions. In summary, EE emerges as a promising strategy to augment cognitive function and decelerate the progression of NDs.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"13"},"PeriodicalIF":4.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of maternal night shift work during pregnancy with DNA methylation in offspring: a meta-analysis in the PACE consortium.","authors":"Irene F Marques, Carola Domènech-Panicello, Madelon L Geurtsen, Thanh T Hoang, Rebecca Richmond, Kristen Polinski, Lea Sirignano, Christian M Page, Anne-Claire Binter, Todd Everson, Amber Burt, Michael Deuschle, Maria Gilles, Fabian Streit, Sunni L Mumford, Per Magnus, Irwin K M Reiss, Marijn J Vermeulen, Stephanie H Witt, Inês Chaves, Edwina Yeung, Stephanie J London, Mònica Guxens, Janine F Felix","doi":"10.1186/s13148-024-01810-y","DOIUrl":"10.1186/s13148-024-01810-y","url":null,"abstract":"<p><strong>Background: </strong>Night shift work during pregnancy has been associated with differential DNA methylation in placental tissue, but no studies have explored this association in cord blood. We aimed to examine associations of maternal night shift work with cord blood DNA methylation.</p><p><strong>Methods: </strong>A total of 4487 mother-newborn pairs from 7 studies were included. Maternal night shift work during pregnancy was ascertained via questionnaires and harmonized into \"any\" versus \"no\". DNA methylation was measured in cord blood using the Illumina Infinium Methylation arrays. Robust linear regression models adjusted for relevant confounders were run in the individual cohorts, and results were meta-analyzed.</p><p><strong>Results: </strong>Maternal night shift work during pregnancy ranged from 3.4% to 26.3%. Three CpGs were differentially methylated in relation to maternal night shift work during pregnancy at a false discovery rate adjusted P < 0.05: cg10945885 (estimate (β) 0.38%, standard error (SE) 0.07), cg00773359 (β 0.25%, SE 0.05), and cg21836426 (β - 0.29%, SE 0.05). Associations of the identified CpGs were found in previous literature for gestational age and childhood and adolescent BMI. In a mouse model of prenatal jet lag exposure, information on offspring DNA methylation of ten homologous genes annotated to the 16 CpGs with P < 1 × 10^-5 in our analysis was available, of which eight were associated (enrichment P: 1.62 × 10^-11).</p><p><strong>Conclusion: </strong>Maternal night shift work during pregnancy was associated with newborn DNA methylation at 3 CpGs. Top findings overlapped with those in a mouse model of gestational jet lag. This work strengthens evidence that DNA methylation could be a marker or mediator of impacts of circadian rhythm disturbances.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"12"},"PeriodicalIF":4.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation profiling at base-pair resolution reveals unique epigenetic features of early-onset colorectal cancer in underrepresented populations.","authors":"Jason Sheng Li, Karen Riggins, Li Yang, Chaorong Chen, Patricia Castro, Wedad Alfarkh, Neda Zarrin-Khameh, Michael E Scheurer, Chad J Creighton, Benjamin Musher, Wei Li, Lanlan Shen","doi":"10.1186/s13148-025-01817-z","DOIUrl":"10.1186/s13148-025-01817-z","url":null,"abstract":"<p><strong>Background: </strong>The incidence of early-onset colorectal cancer (EOCRC) has been rising at an alarming rate in the USA, and EOCRC disproportionately affects racial/ethnic minorities. Here, we construct comprehensive profiles of EOCRC DNA methylomes at base-pair resolution for a cohort of Hispanic and African American patients.</p><p><strong>Results: </strong>We show the epigenetic landscape of these EOCRC patients differs from that of late-onset colorectal cancer patients, and methylation canyons in EOCRC tumor tissue preferentially overlapped genes in cancer-related pathways. Furthermore, we identify epigenetic alterations in metabolic genes that are specific to our racial/ethnic minority EOCRC cohort but not Caucasian patients from TCGA. Top genes differentially methylated between these cohorts included the obesity-protective MFAP2 gene as well as cancer risk susceptibility genes APOL3 and RNASEL.</p><p><strong>Conclusions: </strong>In this study, we provide to the scientific community high-resolution DNA methylomes for a cohort of EOCRC patients from underrepresented populations. Our exploratory findings in this cohort highlight epigenetic mechanisms underlying the pathogenesis of EOCRC and nominate novel biomarkers for EOCRC in underrepresented populations.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"11"},"PeriodicalIF":4.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TET2-mediated 5-hydroxymethylcytosine of TXNIP promotes cell cycle arrest in systemic anaplastic large cell lymphoma.","authors":"Ziqing Yu, Lihua Zhong, Wangyang Tang, Wenfang Zhang, Ting Lin, Weifeng Zhu, Gang Chen, Jianchao Wang","doi":"10.1186/s13148-025-01816-0","DOIUrl":"10.1186/s13148-025-01816-0","url":null,"abstract":"<p><strong>Background: </strong>5-Hydroxymethylcytosine (5hmC) modification represents a significant epigenetic modification within DNA, playing a pivotal role in a range of biological processes associated with various types of cancer. The role of 5hmC in systemic anaplastic large cell lymphoma (ALCL) has not been thoroughly investigated. This study aims to examine the function of 5hmC in the advancement of ALCL.</p><p><strong>Methods: </strong>Formalin-fixed, paraffin-embedded (FFPE) tumor tissues (n = 46) were obtained from ALCL patients. GEO dataset was used to analyze the expression 5hmC-relative enzymes. Immunohistochemistry was conducted to assess the level of 5hmC and Ten-eleven translocation 2 (TET2) on FFPE samples. The ALK-positive cell line, Su-DHL-1, and the ALK-negative cell line, DL-40, were utilized as in vitro experimental models. RNA-sequencing and hMeDIP-sequencing assays were performed to explore the potential functions of TET2 in cell cycle regulation.</p><p><strong>Results: </strong>Our study identified a reduction of 5hmC levels in patients with ALCL, which exhibited a positive correlation with TET2 expression. Downregulation TET2 resulted in decreased 5hmC levels and facilitated the progression of the cell cycle in ALCL cell lines. hMeDIP-seq and subsequent functional analyses demonstrated the involvement of thioredoxin interacting protein (TXNIP) in the regulation of ALCL cells. Further mechanistic studies revealed that 5hmC levels influenced TXNIP expression.</p><p><strong>Conclusions: </strong>Our study underscores the pivotal roles of 5hmC and TET2 in the regulation of cell cycle progression in ALCL. Therapeutic strategies aimed at targeting 5hmC modification or TET2 may offer a novel approach for the management of ALCL.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"10"},"PeriodicalIF":4.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TEC-mediated tRF-31R9J regulates histone lactylation and acetylation by HDAC1 to suppress hepatocyte ferroptosis and improve non-alcoholic steatohepatitis.","authors":"Juanjuan Zhu, Xian Wu, Mao Mu, Quan Zhang, Xueke Zhao","doi":"10.1186/s13148-025-01813-3","DOIUrl":"10.1186/s13148-025-01813-3","url":null,"abstract":"<p><strong>Background: </strong>Tectorigenin (TEC) is a monomer of anthocyanin, which we found exhibits hepatoprotective effects. tRNA-derived fragments (tRFs) and ferroptosis play important roles in the pathogenesis of non-alcoholic steatohepatitis (NASH). Recent discoveries have revealed that histone lactylation and acetylation play a crucial role in connecting cellular metabolism and epigenetic regulation through post-translational modification of histones. However, it is unclear whether TEC improves NASH by regulating histone lactylation, acetylation and hepatocyte ferroptosis through tRFs.</p><p><strong>Results: </strong>In this study, we demonstrated that TEC significantly inhibits free fatty acids-induced hepatocyte ferroptosis both in vitro and in vivo. We identified tRF-31R9J (tRF-31-R9JP9P9NH5HYD) involved in TEC regulation of ferroptosis in steatosis hepatocytes. Overexpression of tRF-31R9J suppressed hepatocyte ferroptosis and enhanced cell viability in steatosis HepG2 cells. Knockdown of tRF-31R9J partially counteracted the inhibitory effect of TEC on ferroptosis in hepatocytes. Mechanistically, tRF-31R9J recruited HDAC1 to reduce the levels of histone lactylation and acetylation modifications of the pro-ferroptosis genes ATF3, ATF4, and CHAC1, thereby inhibiting their gene expression.</p><p><strong>Conclusions: </strong>This study demonstrates that TEC-mediated tRF-31R9J inhibits hepatocyte ferroptosis through HDAC1-regulated histone delactylation and deacetylation, thereby improving NASH. These discoveries offer a theoretical foundation and new strategies for the medical management of NASH.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"9"},"PeriodicalIF":4.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}