Epigenomics最新文献

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Impact of excess sugar on the whole genome DNA methylation pattern in human sperm. 过量糖对人类精子全基因组DNA甲基化模式的影响。
IF 3 4区 医学
Epigenomics Pub Date : 2025-02-01 Epub Date: 2024-12-20 DOI: 10.1080/17501911.2024.2439782
Josefine Jönsson, Alexander Perfilyev, Unn Kugelberg, Signe Skog, Axel Lindström, Sabrina Ruhrmann, Jones K Ofori, Karl Bacos, Tina Rönn, Anita Öst, Charlotte Ling
{"title":"Impact of excess sugar on the whole genome DNA methylation pattern in human sperm.","authors":"Josefine Jönsson, Alexander Perfilyev, Unn Kugelberg, Signe Skog, Axel Lindström, Sabrina Ruhrmann, Jones K Ofori, Karl Bacos, Tina Rönn, Anita Öst, Charlotte Ling","doi":"10.1080/17501911.2024.2439782","DOIUrl":"10.1080/17501911.2024.2439782","url":null,"abstract":"<p><strong>Aims, patients & methods: </strong>Dietary factors may regulate the epigenome. We aimed to explore whether a diet intervention, including excess sugar, affects the methylome in human sperm, and to describe the sperm methylome. We used Whole Genome Bisulfite Sequencing (WGBS) to analyze DNA methylation in sperm taken at three time points from 15 males during a diet intervention; i) at baseline, ii) after one week on a standardized diet, and iii) after an additional week on a high-sugar diet providing 150% of their estimated total energy expenditure.</p><p><strong>Results: </strong>We identified seven nominal diet-associated differentially methylated regions in sperm (<i>p</i> < 0.05). The diet was nominally associated with methylation of 143 sites linked to fertility (e.g. <i>AHRR</i>, <i>GNAS</i>, and <i>HDAC4</i>), 313 sites in imprinted genes (e.g. <i>GLIS3</i>, <i>PEG10</i>, <i>PEG3</i>, and <i>SNURF</i>), and 42 sites in top 1%-expressed genes (e.g. <i>CHD2</i>) (<i>p</i> < 0.05). In sperm, 3'UTRs and introns had the highest levels of methylation, while 5'UTRs and CpG islands had the lowest levels. Non-expressed genes in human sperm were hypomethylated in exons compared with transcribed genes.</p><p><strong>Conclusions: </strong>In human sperm, DNA methylation levels were linked to gene expression, and excess sugar had modest effects on methylation on imprinted and highly expressed genes, and genes affecting fertility.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"89-104"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871674","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
EZH2 inhibition enhances the activity of Carboplatin in aggressive-variant prostate cancer cell lines. EZH2抑制可增强卡铂在侵袭性前列腺癌细胞系中的活性。
IF 3 4区 医学
Epigenomics Pub Date : 2025-02-01 Epub Date: 2025-01-29 DOI: 10.1080/17501911.2025.2453419
Maryam Latarani, Perla Pucci, Mark Eccleston, Massimiliano Manzo, Priyadarsini Gangadharannambiar, Irene Fischetti, Ilaria Alborelli, Vera Mongiardini, Namra Mahmood, Mario Paolo Colombo, Benedetto Grimaldi, Sushila Rigas, Shusuke Akamatsu, Cheryl Hawkes, Yuzhuo Wang, Elena Jachetti, Francesco Crea
{"title":"EZH2 inhibition enhances the activity of Carboplatin in aggressive-variant prostate cancer cell lines.","authors":"Maryam Latarani, Perla Pucci, Mark Eccleston, Massimiliano Manzo, Priyadarsini Gangadharannambiar, Irene Fischetti, Ilaria Alborelli, Vera Mongiardini, Namra Mahmood, Mario Paolo Colombo, Benedetto Grimaldi, Sushila Rigas, Shusuke Akamatsu, Cheryl Hawkes, Yuzhuo Wang, Elena Jachetti, Francesco Crea","doi":"10.1080/17501911.2025.2453419","DOIUrl":"10.1080/17501911.2025.2453419","url":null,"abstract":"<p><strong>Background: </strong>Aggressive Variant Prostate Cancers (AVPCs) are incurable malignancies. Platinum-based chemotherapies are used for the palliative treatment of AVPC. The Polycomb Repressive Complex 2 (PRC2) promotes prostate cancer progression <i>via</i> histone H3 Lysine 27 tri-methylation (H3K27me3). <i>EZH2</i> encodes the catalytic subunit of PRC2. A recently developed nucleosome capture technology (Nu.Q<sup>Ⓡ</sup>).measures H3K27me3 levels in biological fluids. EZH2 inhibitors (EZH2i) are being tested in clinical trials. We hypothesize that epigenetic reprogramming <i>via</i> EZH2i improves the efficacy of Carboplatin in AVPC and that EZH2i activity can be measured via both cellular- and cell-free nucleosomal H3K27me3 (cf-H3K27me3) levels.</p><p><strong>Methods: </strong>We studied the expression of PRC2 genes in clinical prostate cancer cohorts (bioinformatics). We determined the effect of EZH2i on cellular- and cf-H3K27me3 levels. We measured dose-dependent effects of Carboplatin with/without EZH2i on AVPC cell viability (IC<sub>50</sub>). We used RNA-Seq to study how EZH2i modulates gene expression in AVPC cells.</p><p><strong>Results: </strong>PRC2 genes were significantly up-regulated in AVPC <i>vs</i> other prostate cancer types. EZH2i reduced both cellular and cf-H3K27me3 levels. EZH2i significantly reduced Carboplatin IC<sub>50</sub>. EZH2i reduced the expression of DNA repair genes and increased the expression of p53-dependent pro-apoptotic factors.</p><p><strong>Conclusions: </strong>EZH2i plus Carboplatin is a promising combination treatment for AVPC.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"145-154"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058573","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
Combined replacement of lnc-MEG3 and miR-155 elicit tumor suppression in multiple myeloma. lnc-MEG3和miR-155联合替代可抑制多发性骨髓瘤的肿瘤。
IF 3 4区 医学
Epigenomics Pub Date : 2025-02-01 Epub Date: 2025-01-16 DOI: 10.1080/17501911.2025.2453413
Nashwa El-Khazragy, Sara Elsayed Abdelrahman, Amal Darwish, Eman H A Hemida
{"title":"Combined replacement of lnc-MEG3 and miR-155 elicit tumor suppression in multiple myeloma.","authors":"Nashwa El-Khazragy, Sara Elsayed Abdelrahman, Amal Darwish, Eman H A Hemida","doi":"10.1080/17501911.2025.2453413","DOIUrl":"10.1080/17501911.2025.2453413","url":null,"abstract":"<p><strong>Aims: </strong>To investigate the biological impact of simultaneous overexpression of lncRNA MEG3 and miR-155, termed a \"double hit,\" on multiple myeloma (MM) cells compared to individual biomarker substitution.</p><p><strong>Materials and methods: </strong>Human MM cells were transfected with MEG3-overexpressed plasmids and miR-155 mimics. Cell cytotoxicity, apoptosis, and gene expression were evaluated in transfected cells and clinical samples.</p><p><strong>Results: </strong>MEG3 and miR-155 were significantly downregulated in MM patients, with lower expression levels correlating with advanced disease stages and poorer survival. Dual overexpression induced potent cytotoxic effects in MM cells.</p><p><strong>Conclusion: </strong>MEG3 and miR-155 are potential tumor suppressors in MM. Simultaneous overexpression of both biomarkers could represent a novel therapeutic strategy, and their levels could serve as diagnostic and prognostic markers.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"167-177"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11816889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002516","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
PX-12 modulates vorinostat-induced acetylation and methylation marks in CAL 27 cells. PX-12调节vorinostat诱导的CAL 27细胞乙酰化和甲基化标记。
IF 3 4区 医学
Epigenomics Pub Date : 2025-02-01 Epub Date: 2024-12-23 DOI: 10.1080/17501911.2024.2441652
Rafia Akhlaq, Tehmina Ahmed, Tajwali Khan, Syed Usama Yaseen Jeelani, Jazmine-Saskya N Joseph-Chowdhury, Simone Sidoli, Syed Ghulam Musharraf, Arslan Ali
{"title":"PX-12 modulates vorinostat-induced acetylation and methylation marks in CAL 27 cells.","authors":"Rafia Akhlaq, Tehmina Ahmed, Tajwali Khan, Syed Usama Yaseen Jeelani, Jazmine-Saskya N Joseph-Chowdhury, Simone Sidoli, Syed Ghulam Musharraf, Arslan Ali","doi":"10.1080/17501911.2024.2441652","DOIUrl":"10.1080/17501911.2024.2441652","url":null,"abstract":"<p><strong>Aim: </strong>The hypoxic tumor microenvironment (TME) in oral squamous cell carcinoma (OSCC) is primarily regulated by hypoxia-inducible factor-1 alpha (HIF-1α), impacting histone acetylation and methylation, which contribute to drug resistance. Vorinostat, a histone deacetylase inhibitor (HDACi), de-stabilizes HIF-1α, while PX-12, a thioredoxin-1 (Trx-1) inhibitor, prevents HIF-1α accumulation. Combining HDACi with a Trx-1 inhibitor may enhance efficacy and reduce resistance by increasing reactive oxygen species (ROS) in cancer cells. This study examines how PX-12 influences vorinostat-induced histone modifications under hypoxia in the OSCC cell line CAL 27 using mass spectrometry.</p><p><strong>Materials and methods: </strong>The OSCC cell line CAL 27 was used to assess histone post-translational modifications induced by PX-12 and Vorinostat under hypoxic conditions through mass spectrometry.</p><p><strong>Results: </strong>The proteomic analysis (ProteomeXchange identifier PXD053244) revealed several crucial histone marks, such as H3K4me1, H3K9ac, H3K9me, H3K14ac, H3K27me, H3K36me, H4K12Ac, and H4K16ac. Along with site-specific histone modifications, exposure of cells to vorinostat and PX-12 alone or in combination affects the global acetylation and methylation levels under hypoxia.</p><p><strong>Conclusion: </strong>Mass spectrometry-based proteomics highlighted the impact of vorinostat and PX-12 on histone acetylation and methylation, offering valuable insights into the epigenetic mechanisms in OSCC and paving a way for epigenetic-based oral cancer therapeutics.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"79-87"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881625","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
Blocking RPA-based methods for the determination of CpG methylation status and detection of gene mutations. 基于阻断rpa的方法测定CpG甲基化状态和检测基因突变。
IF 3 4区 医学
Epigenomics Pub Date : 2025-02-01 Epub Date: 2024-12-29 DOI: 10.1080/17501911.2024.2447810
Mina Ishidoya, Toshitsugu Fujita, Hodaka Fujii
{"title":"Blocking RPA-based methods for the determination of CpG methylation status and detection of gene mutations.","authors":"Mina Ishidoya, Toshitsugu Fujita, Hodaka Fujii","doi":"10.1080/17501911.2024.2447810","DOIUrl":"10.1080/17501911.2024.2447810","url":null,"abstract":"","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":"17 3","pages":"141-143"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390565","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
The role of lncRNAs in the interplay of signaling pathways and epigenetic mechanisms in glioma. lncrna在胶质瘤中信号通路相互作用和表观遗传机制中的作用。
IF 3 4区 医学
Epigenomics Pub Date : 2025-02-01 Epub Date: 2025-01-19 DOI: 10.1080/17501911.2024.2442297
Can Bora Yildiz, Jian Du, K Naga Mohan, Geraldine Zimmer-Bensch, Sara Abdolahi
{"title":"The role of lncRNAs in the interplay of signaling pathways and epigenetic mechanisms in glioma.","authors":"Can Bora Yildiz, Jian Du, K Naga Mohan, Geraldine Zimmer-Bensch, Sara Abdolahi","doi":"10.1080/17501911.2024.2442297","DOIUrl":"10.1080/17501911.2024.2442297","url":null,"abstract":"<p><p>Gliomas, highly aggressive tumors of the central nervous system, present overwhelming challenges due to their heterogeneity and therapeutic resistance. Glioblastoma multiforme (GBM), the most malignant form, underscores this clinical urgency due to dismal prognosis despite aggressive treatment regimens. Recent advances in cancer research revealed signaling pathways and epigenetic mechanisms that intricately govern glioma progression, offering multifaceted targets for therapeutic intervention. This review explores the dynamic interplay between signaling events and epigenetic regulation in the context of glioma, with a particular focus on the crucial roles played by non-coding RNAs (ncRNAs). Through direct and indirect epigenetic targeting, ncRNAs emerge as key regulators shaping the molecular landscape of glioblastoma across its various stages. By dissecting these intricate regulatory networks, novel and patient-tailored therapeutic strategies could be devised to improve patient outcomes with this devastating disease.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"125-140"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001747","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
Insights to aging prediction with AI based epigenetic clocks. 利用基于人工智能的表观遗传时钟洞察衰老预测。
IF 3 4区 医学
Epigenomics Pub Date : 2025-01-01 Epub Date: 2024-11-25 DOI: 10.1080/17501911.2024.2432854
Joshua J Levy, Alos B Diallo, Marietta K Saldias Montivero, Sameer Gabbita, Lucas A Salas, Brock C Christensen
{"title":"Insights to aging prediction with AI based epigenetic clocks.","authors":"Joshua J Levy, Alos B Diallo, Marietta K Saldias Montivero, Sameer Gabbita, Lucas A Salas, Brock C Christensen","doi":"10.1080/17501911.2024.2432854","DOIUrl":"10.1080/17501911.2024.2432854","url":null,"abstract":"<p><p>Over the past century, human lifespan has increased remarkably, yet the inevitability of aging persists. The disparity between biological age, which reflects pathological deterioration and disease, and chronological age, indicative of normal aging, has driven prior research focused on identifying mechanisms that could inform interventions to reverse excessive age-related deterioration and reduce morbidity and mortality. DNA methylation has emerged as an important predictor of age, leading to the development of epigenetic clocks that quantify the extent of pathological deterioration beyond what is typically expected for a given age. Machine learning technologies offer promising avenues to enhance our understanding of the biological mechanisms governing aging by further elucidating the gap between biological and chronological ages. This perspective article examines current algorithmic approaches to epigenetic clocks, explores the use of machine learning for age estimation from DNA methylation, and discusses how refining the interpretation of ML methods and tailoring their inferences for specific patient populations and cell types can amplify the utility of these technologies in age prediction. By harnessing insights from machine learning, we are well-positioned to effectively adapt, customize and personalize interventions aimed at aging.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"49-57"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Placental expression and methylation of angiogenic factors in assisted reproductive technology pregnancies from India. 印度辅助生殖技术妊娠中胎盘血管生成因子的表达和甲基化。
IF 3 4区 医学
Epigenomics Pub Date : 2025-01-01 Epub Date: 2024-12-10 DOI: 10.1080/17501911.2024.2438593
Deepali Sundrani, Aishwarya Kapare, Himanshi Yadav, Karuna Randhir, Sanjay Gupte, Sadhana Joshi
{"title":"Placental expression and methylation of angiogenic factors in assisted reproductive technology pregnancies from India.","authors":"Deepali Sundrani, Aishwarya Kapare, Himanshi Yadav, Karuna Randhir, Sanjay Gupte, Sadhana Joshi","doi":"10.1080/17501911.2024.2438593","DOIUrl":"10.1080/17501911.2024.2438593","url":null,"abstract":"<p><strong>Aim: </strong>This study aims to examine the gene expression and DNA methylation patterns of angiogenic factors in the placentae of Indian women who underwent assisted reproductive technology (ART) procedures and their association with maternal one-carbon metabolites and birth outcome.</p><p><strong>Methods: </strong>Placental gene expression and DNA methylation of angiogenic factors (<i>VEGF</i>, <i>PlGF</i>, <i>FLT-1</i>, <i>KDR</i>) in Indian women who underwent ART procedures (<i>n</i> = 64) and women who conceived naturally (Non-ART) (<i>n</i> = 93) was investigated using RT-qPCR and Epitect Methyl-II PCR assay kits. Maternal plasma one-carbon metabolites were assessed by CMIA technology.</p><p><strong>Result: </strong>Gene expression of <i>FLT-1</i> and <i>KDR</i> was higher (<i>p</i> < 0.05) in the ART placentae. Placental global DNA methylation levels were higher (<i>p</i> < 0.01) and DNA methylation levels of <i>VEGF</i> promoter were lower (<i>p</i> < 0.05) in ART compared to non-ART women. Maternal plasma folate and vitamin B<sub>12</sub> levels were higher (<i>p</i> < 0.01) in the ART group. Gene expression of <i>PlGF</i> was negatively associated with maternal plasma folate (<i>p</i> < 0.05) whereas KDR was positively associated with maternal plasma homocysteine (<i>p</i> < 0.05). Gene expression of <i>KDR</i> was positively associated with chest circumference of the baby (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>Hypomethylation of <i>VEGF</i> and increased expression of <i>FLT-1</i> and <i>KDR</i> was observed in the placentae of women who underwent ART procedure.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"21-31"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Epigenetic rejuvenation: a journey backwards towards an epigenomic ground state. 表观遗传学返老还童:向表观遗传学基态倒退的旅程。
IF 3 4区 医学
Epigenomics Pub Date : 2025-01-01 Epub Date: 2024-11-25 DOI: 10.1080/17501911.2024.2432851
Nelly N Olova
{"title":"Epigenetic rejuvenation: a journey backwards towards an epigenomic ground state.","authors":"Nelly N Olova","doi":"10.1080/17501911.2024.2432851","DOIUrl":"10.1080/17501911.2024.2432851","url":null,"abstract":"","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"1-3"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multi-omics insights into the pathogenesis of diabetic cardiomyopathy: epigenetic and metabolic profiles. 糖尿病性心肌病发病机制的多组学研究:表观遗传和代谢谱。
IF 3 4区 医学
Epigenomics Pub Date : 2025-01-01 Epub Date: 2024-12-02 DOI: 10.1080/17501911.2024.2435257
Li Zhou, Shuai Mei, Xiaozhu Ma, Qidamugai Wuyun, Ziyang Cai, Chen Chen, Hu Ding, Jiangtao Yan
{"title":"Multi-omics insights into the pathogenesis of diabetic cardiomyopathy: epigenetic and metabolic profiles.","authors":"Li Zhou, Shuai Mei, Xiaozhu Ma, Qidamugai Wuyun, Ziyang Cai, Chen Chen, Hu Ding, Jiangtao Yan","doi":"10.1080/17501911.2024.2435257","DOIUrl":"10.1080/17501911.2024.2435257","url":null,"abstract":"<p><strong>Aim: </strong>Diabetic cardiomyopathy (DbCM), a complex metabolic disease, greatly threatens human health due to therapeutic limitations. Multi-omics approaches facilitate the elucidation of its intrinsic pathological changes.</p><p><strong>Methods: </strong>Metabolomics, RNA-seq, proteomics, and assay of transposase-accessible chromatin (ATAC-seq) were utilized to elucidate multidimensional molecular alterations in DbCM.</p><p><strong>Results: </strong>In the heart and plasma of mice with DbCM, metabolomic analysis demonstrated significant differences in branched-chain amino acids (BCAAs) and lipids. Subsequent RNA-seq and proteomics showed that the key genes, including BCKDHB, PPM1K, Cpt1b, Fabp4, Acadm, Acadl, Acadvl, HADH, HADHA, HADHB, Eci1, Eci2, PDK4, and HMGCS2, were aberrantly regulated, contributing to the disorder of BCAAs and fatty acids. ATAC-seq analysis underscored the pivotal role of epigenetic regulation by revealing dynamic shifts in chromatin accessibility and a robust positive correlation with gene expression patterns in diabetic cardiomyopathy mice. Furthermore, motif analysis identified that KLF15 as a critical transcription factor in DbCM, regulating the core genes implicated with BCAAs metabolism.</p><p><strong>Conclusion: </strong>Our research delved into the metabolic alterations and epigenetic landscape and revealed that KLF15 may be a promising candidate for therapeutic intervention in DbCM.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"33-48"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766149","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
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