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Identification of miR-20b-5p as an inhibitory regulator in cardiac differentiation via TET2 and DNA hydroxymethylation Clin. Epigenet. (IF 5.7) Pub Date : 2024-03-15 Ke-Xin Li, Jia-Ru Li, Sheng-Jia Zuo, Xudong Li, Xian-Tong Chen, Pei-Yi Xiao, Hui-Tao Li, Ling Sun, Tao Qian, Hao-Min Zhang, Dongxing Zhu, Xi-Yong Yu, Guojun Chen, Xue-Yan Jiang
Congenital heart disease (CHD) is a prevalent congenital cardiac malformation, which lacks effective early biological diagnosis and intervention. MicroRNAs, as epigenetic regulators of cardiac development, provide potential biomarkers for the diagnosis and treatment of CHD. However, the mechanisms underlying miRNAs-mediated regulation of cardiac development and CHD malformation remain to be further
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Epigenetic age acceleration and risk of aortic valve stenosis: a bidirectional Mendelian randomization study Clin. Epigenet. (IF 5.7) Pub Date : 2024-03-12 Wanqian Pan, Qi Huang, Le Zhou, Jia Lin, Xiaojiao Du, Xiaodong Qian, Tingbo Jiang, Weixiang Chen
Aortic valve stenosis (AVS) is the most prevalent cardiac valve lesion in developed countries, and pathogenesis is closely related to aging. DNA methylation-based epigenetic clock is now recognized as highly accurate predictor of the aging process and associated health outcomes. This study aimed to explore the causal relationship between epigenetic clock and AVS by conducting a bidirectional Mendelian
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MAL expression downregulation through suppressive H3K27me3 marks at the promoter in HPV16-related cervical cancers is prognostically relevant and manifested by the interplay of novel MAL antisense long noncoding RNA AC103563.8, E7 oncoprotein and EZH2 Clin. Epigenet. (IF 5.7) Pub Date : 2024-03-10 Abarna Sinha, Abhisikta Ghosh, Arnab Ghosh, Sonia Mathai, Jaydip Bhaumik, Asima Mukhopadhyay, Arindam Maitra, Nidhan K. Biswas, Sharmila Sengupta
MAL (T-lymphocyte maturation-associated protein) is highly downregulated in most cancers, including cervical cancer (CaCx), attributable to promoter hypermethylation. Long noncoding RNA genes (lncGs) play pivotal roles in CaCx pathogenesis, by interacting with human papillomavirus (HPV)-encoded oncoproteins, and epigenetically regulating coding gene expression. Hence, we attempted to decipher the impact
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Novel histone post-translational modifications in Alzheimer’s disease: current advances and implications Clin. Epigenet. (IF 5.7) Pub Date : 2024-03-09 Yuanyuan Qin, Ping Yang, Wanhong He, Dongze Li, Lisha Zeng, Junle Li, Tingting Zhou, Juan Peng, Ling Cao, Wei Huang
Alzheimer’s disease (AD) has a complex pathogenesis, and multiple studies have indicated that histone post-translational modifications, especially acetylation, play a significant role in it. With the development of mass spectrometry and proteomics, an increasing number of novel HPTMs, including lactoylation, crotonylation, β-hydroxybutyrylation, 2-hydroxyisobutyrylation, succinylation, and malonylation
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An EWAS of dementia biomarkers and their associations with age, African ancestry, and PTSD Clin. Epigenet. (IF 5.7) Pub Date : 2024-03-02 Mark W. Miller, Erika J. Wolf, Xiang Zhao, Mark W. Logue, Sage E. Hawn
Large-scale cohort and epidemiological studies suggest that PTSD confers risk for dementia in later life but the biological mechanisms underlying this association remain unknown. This study examined this question by assessing the influences of PTSD, APOE ε4 genotypes, DNA methylation, and other variables on the age- and dementia-associated biomarkers Aβ40, Aβ42, GFAP, NfL, and pTau-181 measured in
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Cell-free DNA methylation reveals cell-specific tissue injury and correlates with disease severity and patient outcomes in COVID-19 Clin. Epigenet. (IF 5.7) Pub Date : 2024-03-01 Yuan-Yuan Li, Ming-Ming Yuan, Yuan-Yuan Li, Shan Li, Jing-Dong Wang, Yu-Fei Wang, Qian Li, Jun Li, Rong-Rong Chen, Jin-Min Peng, Bin Du
The recently identified methylation patterns specific to cell type allows the tracing of cell death dynamics at the cellular level in health and diseases. This study used COVID-19 as a disease model to investigate the efficacy of cell-specific cell-free DNA (cfDNA) methylation markers in reflecting or predicting disease severity or outcome. Whole genome methylation sequencing of cfDNA was performed
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DNA methylation may partly explain psychotropic drug-induced metabolic side effects: results from a prospective 1-month observational study Clin. Epigenet. (IF 5.7) Pub Date : 2024-02-28 Céline Dubath, Eleonora Porcu, Aurélie Delacrétaz, Claire Grosu, Nermine Laaboub, Marianna Piras, Armin von Gunten, Philippe Conus, Kerstin Jessica Plessen, Zoltán Kutalik, Chin Bin Eap
Metabolic side effects of psychotropic medications are a major drawback to patients’ successful treatment. Using an epigenome-wide approach, we aimed to investigate DNA methylation changes occurring secondary to psychotropic treatment and evaluate associations between 1-month metabolic changes and both baseline and 1-month changes in DNA methylation levels. Seventy-nine patients starting a weight gain
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Improvements in lung function following vitamin C supplementation to pregnant smokers are associated with buccal DNA methylation at 5 years of age Clin. Epigenet. (IF 5.7) Pub Date : 2024-02-27 Lyndsey E. Shorey-Kendrick, Cindy T. McEvoy, Kristin Milner, Julia Harris, Julie Brownsberger, Robert S. Tepper, Byung Park, Lina Gao, Annette Vu, Cynthia D. Morris, Eliot R. Spindel
We previously reported in the “Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function” randomized clinical trial (RCT) that vitamin C (500 mg/day) supplementation to pregnant smokers is associated with improved respiratory outcomes that persist through 5 years of age. The objective of this study was to assess whether buccal cell DNA methylation (DNAm), as a surrogate for
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Prediction of methylation status using WGS data of plasma cfDNA for multi-cancer early detection (MCED) Clin. Epigenet. (IF 5.7) Pub Date : 2024-02-27 Pin Cui, Xiaozhou Zhou, Shu Xu, Weihuang He, Guozeng Huang, Yong Xiong, Chuxin Zhang, Tingmin Chang, Mingji Feng, Hanming Lai, Yi Pan
Cell-free DNA (cfDNA) contains a large amount of molecular information that can be used for multi-cancer early detection (MCED), including changes in epigenetic status of cfDNA, such as cfDNA fragmentation profile. The fragmentation of cfDNA is non-random and may be related to cfDNA methylation. This study provides clinical evidence for the feasibility of inferring cfDNA methylation levels based on
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Reduced representative methylome profiling of cell-free DNA for breast cancer detection Clin. Epigenet. (IF 5.7) Pub Date : 2024-02-27 Qingmo Yang, Xingqiang Zhu, Yulu Liu, Zhi He, Huan Xu, Hailing Zheng, Zhiming Huang, Dan Wang, Xiaofang Lin, Ping Guo, Hongliang Chen
Whole-genome methylation sequencing of cfDNA is not cost-effective for tumor detection. Here, we introduce reduced representative methylome profiling (RRMP), which employs restriction enzyme for depletion of AT-rich sequence to achieve enrichment and deep sequencing of CG-rich sequences. We first verified the ability of RRMP to enrich CG-rich sequences using tumor cell genomic DNA and analyzed differential
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Epigenetic aging in older people living with HIV in Eswatini: a pilot study of HIV and lifestyle factors and epigenetic aging Clin. Epigenet. (IF 5.7) Pub Date : 2024-02-26 Christian K. Dye, Haotian Wu, Gabriela L. Jackson, Altaye Kidane, Rejoice Nkambule, Nomthandazo G. Lukhele, Bongiwe Prudence Malinga, Rhinos Chekenyere, Wafaa M. El-Sadr, Andrea A. Baccarelli, Tiffany G. Harris
People living with HIV (PLHIV) on effective antiretroviral therapy are living near-normal lives. Although they are less susceptible to AIDS-related complications, they remain highly vulnerable to non-communicable diseases. In this exploratory study of older PLHIV (OPLHIV) in Eswatini, we investigated whether epigenetic aging (i.e., the residual between regressing epigenetic age on chronological age)
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Abnormal DNA methylation within HPA-axis genes years after paediatric critical illness Clin. Epigenet. (IF 5.7) Pub Date : 2024-02-23 Grégoire Coppens, Ilse Vanhorebeek, Fabian Güiza, Inge Derese, Pieter J. Wouters, Arno Téblick, Karolijn Dulfer, Koen F. Joosten, Sascha C. Verbruggen, Greet Van den Berghe
Critically ill children suffer from impaired physical/neurocognitive development 2 years later. Glucocorticoid treatment alters DNA methylation within the hypothalamus–pituitary–adrenal (HPA) axis which may impair normal brain development, cognition and behaviour. We tested the hypothesis that paediatric-intensive-care-unit (PICU) patients, sex- and age-dependently, show long-term abnormal DNA methylation
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Epigenetic regulation and factors that influence the effect of iPSCs-derived neural stem/progenitor cells (NS/PCs) in the treatment of spinal cord injury Clin. Epigenet. (IF 5.7) Pub Date : 2024-02-21 Yubiao Yang, Boyuan Ma, Jinyu Chen, Derong Liu, Jun Ma, Bo Li, Jian Hao, Xianhu Zhou
Spinal cord injury (SCI) is a severe neurological disorder that causes neurological impairment and disability. Neural stem/progenitor cells (NS/PCs) derived from induced pluripotent stem cells (iPSCs) represent a promising cell therapy strategy for spinal cord regeneration and repair. However, iPSC-derived NS/PCs face many challenges and issues in SCI therapy; one of the most significant challenges
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Epigenome-wide association study of dietary fatty acid intake Clin. Epigenet. (IF 5.7) Pub Date : 2024-02-16 Julia Lange de Luna, Aayah Nounu, Sonja Neumeyer, Lucy Sinke, Rory Wilson, Fabian Hellbach, Pamela R. Matías-García, Thomas Delerue, Juliane Winkelmann, Annette Peters, Barbara Thorand, Marian Beekman, Bastiaan T. Heijmans, Eline Slagboom, Christian Gieger, Jakob Linseisen, Melanie Waldenberger
Dietary intake of n-3 polyunsaturated fatty acids (PUFA) may have a protective effect on the development of cardiovascular diseases, diabetes, depression and cancer, while a high intake of n-6 PUFA was often reported to be associated with inflammation-related traits. The effect of PUFAs on health outcomes might be mediated by DNA methylation (DNAm). The aim of our study is to identify the impact of
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Increased CpG methylation at the CDH1 locus in inflamed ileal mucosa of patients with Crohn disease Clin. Epigenet. (IF 5.7) Pub Date : 2024-02-14 Charles de Ponthaud, Solafah Abdalla, Marie-Pierre Belot, Xiaojian Shao, Christophe Penna, Antoine Brouquet, Pierre Bougnères
E-cadherin, a major actor of cell adhesion in the intestinal barrier, is encoded by the CDH1 gene associated with susceptibility to Crohn Disease (CD) and colorectal cancer. Since epigenetic mechanisms are suspected to contribute to the multifactorial pathogenesis of CD, we studied CpG methylation at the CDH1 locus. The methylation of the CpG island (CGI) and of the 1st enhancer, two critical regulatory
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Kidney-specific methylation patterns correlate with kidney function and are lost upon kidney disease progression Clin. Epigenet. (IF 5.7) Pub Date : 2024-02-12 Naor Sagy, Noa Meyrom, Pazit Beckerman, Oren Pleniceanu, Daniel Z. Bar
Chronological and biological age correlate with DNA methylation levels at specific sites in the genome. Linear combinations of multiple methylation sites, termed epigenetic clocks, can inform us the chronological age and predict multiple health-related outcomes. However, why some sites correlating with lifespan, healthspan, or specific medical conditions remain poorly understood. Kidney fibrosis is
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Molecular map of disulfidptosis-related genes in lung adenocarcinoma: the perspective toward immune microenvironment and prognosis Clin. Epigenet. (IF 5.7) Pub Date : 2024-02-11 Fangchao Zhao, Lei Su, Xuefeng Wang, Jiusong Luan, Xin Zhang, Yishuai Li, Shujun Li, Ling Hu
Disulfidptosis is a recently discovered form of programmed cell death that could impact cancer development. Nevertheless, the prognostic significance of disulfidptosis-related genes (DRGs) in lung adenocarcinoma (LUAD) requires further clarification. This study systematically explores the genetic and transcriptional variability, prognostic relevance, and expression profiles of DRGs. Clusters related
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Tissue of origin prediction for cancer of unknown primary using a targeted methylation sequencing panel Clin. Epigenet. (IF 5.7) Pub Date : 2024-02-09 Miaomiao Sun, Bo Xu, Chao Chen, Youjie Zhu, Xiaomo Li, Kuisheng Chen
Cancer of unknown primary (CUP) is a group of rare malignancies with poor prognosis and unidentifiable tissue-of-origin. Distinct DNA methylation patterns in different tissues and cancer types enable the identification of the tissue of origin in CUP patients, which could help risk assessment and guide site-directed therapy. Using genome-wide DNA methylation profile datasets from The Cancer Genome Atlas
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The interaction between DNA methylation and tumor immune microenvironment: from the laboratory to clinical applications Clin. Epigenet. (IF 5.7) Pub Date : 2024-02-08 Daoqi Zhu, Siying Zeng, Chao Su, Jingjun Li, Yiwen Xuan, Yongkai Lin, Enwu Xu, Qin Fan
DNA methylation is a pivotal epigenetic modification that affects gene expression. Tumor immune microenvironment (TIME) comprises diverse immune cells and stromal components, creating a complex landscape that can either promote or inhibit tumor progression. In the TIME, DNA methylation has been shown to play a critical role in influencing immune cell function and tumor immune evasion. DNA methylation
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Correction: A transgenic mice model of retinopathy of cblG‑type inherited disorder of one‑carbon metabolism highlights epigenome‑wide alterations related to cone photoreceptor cells development and retinal metabolism Clin. Epigenet. (IF 5.7) Pub Date : 2024-02-08 Karim Matmat, Jean-Baptiste Conart, Paul-Henri Graindorge, Sandra El Kouche, Ziad Hassan, Youssef Siblini, Rémy Umoret, Ramia Safar, Okan Baspinar, Aurélie Robert, Jean-Marc Alberto, Abderrahim Oussalah, Sébastien Hergalant, David Coelho, Jean-Louis Guéant, Rosa-Maria Guéant-Rodriguez
Correction: Clinical Epigenetics (2023) 15:158 https://doi.org/10.1186/s13148-023-01567-w Following publication of the original article [1], one of the co-author “Sébastien Hergalant“ was omitted in the authorship list. The correct authorship list is: Karim Matmat, Jean-Baptiste Conart, Paul-Henri Graindorge, Sandra El Kouche, Ziad Hassan, Youssef Siblini, Rémy Umoret, Ramia Safar, Okan Baspinar, Aurélie
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Self-control is associated with health-relevant disparities in buccal DNA-methylation measures of biological aging in older adults Clin. Epigenet. (IF 5.7) Pub Date : 2024-02-08 Y. E. Willems, A. deSteiguer, P. T. Tanksley, L. Vinnik, D. Fraemke, A. Okbay, D. Richter, G. G. Wagner, R. Hertwig, P. Koellinger, E. M. Tucker-Drob, K. P. Harden, Laurel Raffington
Self-control is a personality dimension that is associated with better physical health and a longer lifespan. Here, we examined (1) whether self-control is associated with buccal and saliva DNA-methylation (DNAm) measures of biological aging quantified in children, adolescents, and adults, and (2) whether biological aging measured in buccal DNAm is associated with self-reported health. Following preregistered
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Per-cell histone acetylation is associated with terminal differentiation in human T cells Clin. Epigenet. (IF 5.7) Pub Date : 2024-02-06 Cheng Yang, You Li, Yaqiu Hu, Qian Li, Yinghua Lan, Yongguo Li
Epigenetic remodeling at effector gene loci has been reported to be critical in regulating T cell differentiation and function. However, efforts to investigate underlying epigenetic mechanisms that control T cell behaviors have been largely hindered by very limited experimental tools, especially in humans. In this study, we employed a flow cytometric assay to analyze histone acetylation at single-cell
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Epigenetics of prenatal stress in humans: the current research landscape Clin. Epigenet. (IF 5.7) Pub Date : 2024-02-02 Linda Dieckmann, Darina Czamara
Fetal exposure to prenatal stress can have significant consequences on short- and long-term health. Epigenetic mechanisms, especially DNA methylation (DNAm), are a possible process how these adverse environmental events could be biologically embedded. We evaluated candidate gene as well as epigenome-wide association studies associating prenatal stress and DNAm changes in peripheral tissues; however
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Identification of DNA methylation biomarkers for evaluating cardiovascular disease risk from epigenome profiles altered by low-dose ionizing radiation Clin. Epigenet. (IF 5.7) Pub Date : 2024-02-01 Jihye Park, Hae-June Lee, Yu Kyeong Han, Keunsoo Kang, Joo Mi Yi
Environmental exposure, medical diagnostic and therapeutic applications, and industrial utilization of radionuclides have prompted a growing focus on the risks associated with low-dose radiation (< 100 mGy). Current evidence suggests that such radiation can induce epigenetic changes. Nevertheless, whether exposure to low-dose radiation can disrupt endothelial cell function at the molecular level is
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METTL3 promotes osteoblast ribosome biogenesis and alleviates periodontitis Clin. Epigenet. (IF 5.7) Pub Date : 2024-01-24 Yiwen Zhang, Yiping Kong, Wenjie Zhang, Jinlin He, Zhanqi Zhang, Yongjie Cai, Yiqing Zhao, Qiong Xu
Periodontitis is a highly prevalent oral disease characterized by bacterium-induced periodontal inflammation and alveolar bone destruction. Osteoblast function is impaired in periodontitis with a global proteome change. METTL3 is the pivotal methyltransferase of N6-methyladenosine (m6A) that is recently proved to exert a crucial role in osteoblast differentiation. This study aims to investigate the
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MethScore as a new comprehensive DNA methylation-based value refining the prognosis in acute myeloid leukemia Clin. Epigenet. (IF 5.7) Pub Date : 2024-01-22 Šárka Šestáková, Cyril Šálek, Dávid Kundrát, Ela Cerovská, Jan Vydra, Ivana Ježíšková, Adam Folta, Jiří Mayer, Petr Cetkovský, Hana Remešová
Changes in DNA methylation are common events in the pathogenesis of acute myeloid leukemia (AML) and have been repeatedly reported as associated with prognosis. However, studies integrating these numerous and potentially prognostically relevant DNA methylation changes are lacking. Therefore, we aimed for an overall evaluation of these epigenetic aberrations to provide a comprehensive NGS-based approach
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The predictive value of BTG1 for the response of newly diagnosed acute myeloid leukemia to decitabine Clin. Epigenet. (IF 5.7) Pub Date : 2024-01-22 Yi Li, Xia Mao, Mengyuan Li, Li Li, Xiwen Tong, Lifang Huang
Decitabine has been widely used to treat acute myeloid leukemia (AML); however as AML is a heterogeneous disease, not all patients benefit from decitabine. This study aimed to identify markers for predicting the response to decitabine. An intersection of in vitro experiments and bioinformatics was performed using a combination of epigenetic and transcriptomic analysis. A tumor-suppressor gene associated
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Integrative analysis identifies gene signatures mediating the effect of DNA methylation on asthma severity and lung function Clin. Epigenet. (IF 5.7) Pub Date : 2024-01-20 Eskezeia Y. Dessie, Lili Ding, Tesfaye B. Mersha
DNA methylation (DNAm) changes play a key role in regulating gene expression in asthma. To investigate the role of epigenetics and transcriptomics change in asthma, we used publicly available DNAm (asthmatics, n = 96 and controls, n = 46) and gene expression (asthmatics, n = 79 and controls, n = 39) data derived from bronchial epithelial cells (BECs). We performed differential methylation/expression
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YAP represses intestinal inflammation through epigenetic silencing of JMJD3 Clin. Epigenet. (IF 5.7) Pub Date : 2024-01-20 Hua Zhu, Jiali Lu, MingYue Fu, Ping Chen, Yali Yu, Min Chen, Qiu Zhao, Min Wu, Mei Ye
Epigenetics plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Some studies have reported that YAP is involved in inflammatory response and can regulate target genes through epigenetic modifications. JMJD3, a histone H3K27me3 demethylase, is associated with some inflammatory diseases. In this study, we investigated the role of YAP in the development of IBD and the underlying
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Pancreatic cancer acquires resistance to MAPK pathway inhibition by clonal expansion and adaptive DNA hypermethylation Clin. Epigenet. (IF 5.7) Pub Date : 2024-01-16 Laura K. Godfrey, Jan Forster, Sven-Thorsten Liffers, Christopher Schröder, Johannes Köster, Leonie Henschel, Kerstin U. Ludwig, David Lähnemann, Marija Trajkovic-Arsic, Diana Behrens, Aldo Scarpa, Rita T. Lawlor, Kathrin E. Witzke, Barbara Sitek, Steven A. Johnsen, Sven Rahmann, Bernhard Horsthemke, Michael Zeschnigk, Jens T. Siveke
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor prognosis. It is marked by extraordinary resistance to conventional therapies including chemotherapy and radiation, as well as to essentially all targeted therapies evaluated so far. More than 90% of PDAC cases harbor an activating KRAS mutation. As the most common KRAS variants in PDAC remain undruggable so far, it seemed promising
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Activation of γ-globin expression by LncRNA-mediated ERF promoter hypermethylation in β-thalassemia Clin. Epigenet. (IF 5.7) Pub Date : 2024-01-13 Xiuqin Bao, Yuanyi Gao, Zhongju Wang, Yuhua Ye, Diyu Chen, Yangjin Zuo, Cunyou Zhao, Xiangmin Xu
The mechanism that drives the switch from fetal to adult hemoglobin (Hb) provides a therapeutic target for β-thalassemia. We have previously identified that hypermethylation of transcription factor ERF promoter reactivated γ-globin expression. To uncover the mechanism underlying the hypermethylation of ERF promoter, we performed RNA sequencing in β0/β0-thalassemia patients and identified an upregulated
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EBV DNA methylation profiles and its application in distinguishing nasopharyngeal carcinoma and nasal NK/T-cell lymphoma Clin. Epigenet. (IF 5.7) Pub Date : 2024-01-11 Cao-Li Tang, Xi-Zhao Li, Ting Zhou, Chang-Mi Deng, Cheng-Tao Jiang, Yu-Meng Zhang, Ying Liao, Tong-Min Wang, Yong-Qiao He, Wen-Qiong Xue, Wei-Hua Jia, Xiao-Hui Zheng
As an oncovirus, EBV is associated with multiple cancers, including solid tumors and hematological malignancies. EBV methylation plays an important role in regulating tumor occurrence. However, the EBV methylation profiles in EBV-associated tumor tissues are poorly understood. In this study, EBV methylation capture sequencing was conducted in several different tumor tissue samples, including NPC, EBVaGC
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Long non-coding RNA ACTA2-AS1 suppresses metastasis of papillary thyroid cancer via regulation of miR-4428/KLF9 axis Clin. Epigenet. (IF 5.7) Pub Date : 2024-01-09 Shuhui Wu, Jingjing Zhu, Tingting Jiang, Ting Cui, Qi Zuo, Guibin Zheng, Guojun Li, Jieyu Zhou, Xiang Chen
Metastasis is the primary cause of recurrence and death in patients with papillary thyroid carcinoma (PTC). LncRNA ACTA2-AS1, a long non-coding RNA, acts as a tumor suppressor in multiple types of human malignancies, while the role of ACTA2-AS1 in PTC metastasis remains unclear. The ACTA2-AS1 expression in PTC tissues was analyzed. The sponged roles of ACTA2-AS1 via miR-4428/KLF9 axis were identified
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Malignant peripheral nerve sheath tumor (MPNST) and MPNST-like entities are defined by a specific DNA methylation profile in pediatric and juvenile population Clin. Epigenet. (IF 5.7) Pub Date : 2024-01-04 Sara Patrizi, Evelina Miele, Lorenza Falcone, Silvia Vallese, Sabrina Rossi, Sabina Barresi, Isabella Giovannoni, Lucia Pedace, Claudia Nardini, Ilaria Masier, Luana Abballe, Antonella Cacchione, Ida Russo, Angela Di Giannatale, Valentina Di Ruscio, Claudia Maria Salgado, Angela Mastronuzzi, Andrea Ciolfi, Marco Tartaglia, Giuseppe Maria Milano, Franco Locatelli, Rita Alaggio
Malignant peripheral nerve sheath tumors (MPNSTs) account for 3–10% of pediatric sarcomas, 50% of which occur in neurofibromatosis type 1 (NF1). Sporadic MPNSTs diagnosis may be challenging due to the absence of specific markers, apart from immunohistochemical H3K27me3 loss. DNA methylation (DNAm) profiling is a useful tool for brain and mesenchymal neoplasms categorization, and MPNSTs exhibit a specific
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Histone acetylation: a key determinant of acquired cisplatin resistance in cancer Clin. Epigenet. (IF 5.7) Pub Date : 2024-01-03 Abhiram Natu, Tripti Verma, Bharat Khade, Rahul Thorat, Poonam Gera, Sangita Dhara, Sanjay Gupta
Cisplatin is an alkylating class of chemotherapeutic drugs used to treat cancer patients. However, cisplatin fails in long-term treatment, and drug resistance is the primary reason for tumor recurrence. Hence, understanding the mechanism of acquirement of chemoresistance is essential for developing novel combination therapeutic approaches. In this study, in vitro cisplatin-resistant cancer cell line
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Exploring the therapeutic potential of Sirt6-enriched adipose stem cell-derived exosomes in myocardial ischemia–reperfusion injury: unfolding new epigenetic frontiers Clin. Epigenet. (IF 5.7) Pub Date : 2024-01-03 Kun Liu, Hecheng Wang, Yiou Wang, Xiaoxu Zhang, Ruihu Wang, Zhaoxuan Zhang, Jian Wang, Xinran Lu, Xiaoyu Wu, Yanshuo Han
The management of myocardial ischemia–reperfusion injury (MIRI) presents continuous therapeutic challenges. NAD-dependent deacetylase Sirtuin 6 (Sirt6) plays distinct roles in various disease contexts and is hence investigated for potential therapeutic applications for MIRI. This study aimed to examine the impact of Sirt6-overexpressing exosomes derived from adipose stem cells (S-ASC-Exo) on MIRI,
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TET2-mediated ECM1 hypomethylation promotes the neovascularization in active proliferative diabetic retinopathy Clin. Epigenet. (IF 5.7) Pub Date : 2024-01-03 Chunyang Cai, Chufeng Gu, Shuai He, Chunren Meng, Dongwei Lai, Jingfa Zhang, Qinghua Qiu
Studies have shown that tet methylcytosine dioxygenase 2 (TET2) is highly expressed in diabetic retinopathy (DR), which reduces the DNA methylation of downstream gene promoters and activates the transcription. Abnormally expressed TET2 and downstream genes in a high-glucose environment are associated with retinal capillary leakage and neovascularization. Here, we investigated the downstream genes of
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Tumor microenvironment deconvolution identifies cell-type-independent aberrant DNA methylation and gene expression in prostate cancer Clin. Epigenet. (IF 5.7) Pub Date : 2024-01-03 Samuel R. Reynolds, Ze Zhang, Lucas A. Salas, Brock C. Christensen
Among men, prostate cancer (PCa) is the second most common cancer and the second leading cause of cancer death. Etiologic factors associated with both prostate carcinogenesis and somatic alterations in tumors are incompletely understood. While genetic variants associated with PCa have been identified, epigenetic alterations in PCa are relatively understudied. To date, DNA methylation (DNAm) and gene
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Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence Clin. Epigenet. (IF 5.7) Pub Date : 2024-01-03 Ivona Bečeheli, Marina Horvatiček, Maja Perić, Barbara Nikolić, Cyrielle Holuka, Marija Klasić, Marina Ivanišević, Mirta Starčević, Gernot Desoye, Dubravka Hranilović, Jonathan D. Turner, Jasminka Štefulj
Serotonin (5-hydroxytryptamine, 5-HT) signaling is involved in neurodevelopment, mood regulation, energy metabolism, and other physiological processes. DNA methylation plays a significant role in modulating the expression of genes responsible for maintaining 5-HT balance, such as 5-HT transporter (SLC6A4), monoamine oxidase A (MAOA), and 5-HT receptor type 2A (HTR2A). Maternal metabolic health can
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MC180295 is a highly potent and selective CDK9 inhibitor with preclinical in vitro and in vivo efficacy in cancer Clin. Epigenet. (IF 5.7) Pub Date : 2024-01-03 Hanghang Zhang, Chen Huang, John Gordon, Sijia Yu, George Morton, Wayne Childers, Magid Abou-Gharbia, Yi Zhang, Jaroslav Jelinek, Jean-Pierre J. Issa
Inhibition of cyclin-dependent kinase 9 (CDK9), a novel epigenetic target in cancer, can reactivate epigenetically silenced genes in cancer by dephosphorylating the SWI/SNF chromatin remodeler BRG1. Here, we characterized the anti-tumor efficacy of MC180295, a newly developed CDK9 inhibitor. In this study, we explored the pharmacokinetics of MC180295 in mice and rats, and tested the anti-tumor efficacy
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Correction: METTL3 exerts synergistic effects on m6A methylation and histone modification to regulate the function of VGF in lung adenocarcinoma Clin. Epigenet. (IF 5.7) Pub Date : 2024-01-02 Kesong Shi, Rula Sa, Le Dou, Yuan Wu, Zhiqiang Dong, Xinyao Fu, Haiquan Yu
Correction : Clinical Epigenetics (2023) 15:153 https://doi.org/10.1186/s13148-023-01568-9 Following publication of the original article [1], the authors noticed the errors in the figure. In Fig. 6D (si-NC 24 h) and Fig. 6D (si-METTL3-2 48 h) are identical, which was an inadvertent mistake by the author. The authors regret for the error and provided revised Fig. 6. This error has been corrected with
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Tangshen formula improves diabetic nephropathy in STZ-induced diabetes rats fed with hyper-methionine by regulating the methylation status of kidney Clin. Epigenet. (IF 5.7) Pub Date : 2024-01-02 Yongwei Jiang, GuoXiong Deng, Chengyin Liu, Han Tang, Jing Zheng, Xiaomu Kong, Meimei Zhao, Yi Liu, Peng Gao, Tianbao Li, Hailing Zhao, Yongtong Cao, Ping Li, Liang Ma
The objective of this study was to examine and analyze differential methylation profiles in order to investigate the influence of hyper-methioninemia (HM) on the development of diabetic nephropathy (DN). Male Wistar rats, aged eight weeks and weighing 250–300 g, were randomly assigned into four groups: a control group (Healthy, n = 8), streptozocin-induced rats (STZ group, n = 8), HM + STZ group (n = 8)
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In-silico guided chemical exploration of KDM4A fragments hits Clin. Epigenet. (IF 5.7) Pub Date : 2023-12-21 Jessica Lombino, Rosario Vallone, Maura Cimino, Maria Rita Gulotta, Giada De Simone, Maria Agnese Morando, Raffaele Sabbatella, Simona Di Martino, Mario Fogazza, Federica Sarno, Claudia Coronnello, Maria De Rosa, Chiara Cipollina, Lucia Altucci, Ugo Perricone, Caterina Alfano
Lysine demethylase enzymes (KDMs) are an emerging class of therapeutic targets, that catalyse the removal of methyl marks from histone lysine residues regulating chromatin structure and gene expression. KDM4A isoform plays an important role in the epigenetic dysregulation in various cancers and is linked to aggressive disease and poor clinical outcomes. Despite several efforts, the KDM4 family lacks
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A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide Clin. Epigenet. (IF 5.7) Pub Date : 2023-12-20 Prodromos Chatzikyriakou, Dimitria Brempou, Mark Quinn, Lauren Fishbein, Roberta Noberini, Ioannis N. Anastopoulos, Nicola Tufton, Eugenie S. Lim, Rupert Obholzer, Johnathan G. Hubbard, Mufaddal Moonim, Tiziana Bonaldi, Katherine L. Nathanson, Louise Izatt, Rebecca J. Oakey
Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours. Pathogenic variants have been identified in more than 15 susceptibility genes; associated tumours are grouped into three Clusters, reinforced by their transcriptional profiles. Cluster 1A PPGLs have pathogenic variants affecting enzymes of the tricarboxylic acid cycle, including succinate dehydrogenase. Within inherited
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A targeted long-read sequencing approach questions the association of OXTR methylation with high-functioning autism Clin. Epigenet. (IF 5.7) Pub Date : 2023-12-20 Jelte Wieting, Kirsten Jahn, Stefan Bleich, Helge Frieling, Maximilian Deest
DNA sequence variation and altered epigenetic regulation of the oxytocin receptor gene (OXTR) have been implicated in autism and autistic-like behaviors. While previous studies have examined subsegments of OXTR, nanopore Cas9-targeted sequencing (nCATS) allows deep characterization of entire genes with simultaneous assessment of epigenetic 5-methylcytosine (5mC) modification and without the need for
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Transcriptome-wide map of N6-methyladenosine (m6A) profiling in coronary artery disease (CAD) with clopidogrel resistance Clin. Epigenet. (IF 5.7) Pub Date : 2023-12-15 Ruoyan Yu, Qinglin Yu, Zhenwei Li, Jiyi Li, Jin Yang, Yingchu Hu, Nan Zheng, Xiaojin Li, Yudie Song, Jiahui Li, Xiaomin Chen, Weiping Du, Jia Su
Clopidogrel resistance profoundly increases the risk of major cardiovascular events in coronary artery disease (CAD) patients. Here, we comprehensively analyse global m6A modification alterations in clopidogrel-resistant (CR) and non-CR patients. After RNA isolation, the RNA transcriptome expression (lncRNA, circRNA, and mRNA) was analysed via RNA-seq, and m6A peaks were identified by MeRIP-seq. The
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ZEB1 hypermethylation is associated with better prognosis in patients with colon cancer Clin. Epigenet. (IF 5.7) Pub Date : 2023-12-13 Irene Fernandez-De-Los-Reyes, Marisa Gomez-Dorronsoro, Iñaki Monreal-Santesteban, Agustín Fernandez-Fernandez, Mario Fraga, Pablo Azcue, Laura Alonso, Beatriz Fernandez-Marlasca, Javier Suarez, Alicia Cordoba-Iturriagagoitia, David Guerrero-Setas
Colon cancer (CC) is a heterogeneous disease that is categorized into four Consensus Molecular Subtypes (CMS) according to gene expression. Patients with loco-regional CC (stages II/III) lack prognostic factors, making it essential to analyze new molecular markers that can delineate more aggressive tumors. Aberrant methylation of genes that are essential in crucial mechanisms such as epithelial mesenchymal
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Histone demethylase KDM4B accelerates the progression of glioblastoma via the epigenetic regulation of MYC stability Clin. Epigenet. (IF 5.7) Pub Date : 2023-12-13 Zhongze Wang, Huarui Cai, Zekun Li, Wei Sun, Erhu Zhao, Hongjuan Cui
Glioblastoma (GBM) is the most malignant and invasive human brain tumor. Histone demethylase 4B (KDM4B) is abnormally expressed in GBM, but the molecular mechanisms by which KDM4B affects the malignant tumor progression are not well defined. GBM cell lines and xenograft tumor samples were subjected to quantitative PCR (qPCR), Western blot, immunohistochemical staining (IHC), as well as ubiquitination
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Methylation analysis by targeted bisulfite sequencing in large for gestational age (LGA) newborns: the LARGAN cohort Clin. Epigenet. (IF 5.7) Pub Date : 2023-12-13 Tamara Carrizosa-Molina, Natalia Casillas-Díaz, Iris Pérez-Nadador, Claudia Vales-Villamarín, Miguel Ángel López-Martínez, Rosa Riveiro-Álvarez, Larry Wilhelm, Rita Cervera-Juanes, Carmen Garcés, Alejandro Lomniczi, Leandro Soriano-Guillén
In 1990, David Barker proposed that prenatal nutrition is directly linked to adult cardiovascular disease. Since then, the relationship between adult cardiovascular risk, metabolic syndrome and birth weight has been widely documented. Here, we used the TruSeq Methyl Capture EPIC platform to compare the methylation patterns in cord blood from large for gestational age (LGA) vs adequate for gestational
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Alterations in DNA methylation associate with reduced migraine and headache days after medication withdrawal treatment in chronic migraine patients: a longitudinal study Clin. Epigenet. (IF 5.7) Pub Date : 2023-12-12 Divya Mehta, Irene de Boer, Heidi G. Sutherland, Judith A. Pijpers, Charlene Bron, Charlotte Bainomugisa, Larisa M. Haupt, Arn M. J. M. van den Maagdenberg, Lyn R. Griffiths, Dale R. Nyholt, Gisela M. Terwindt
Chronic migraine, a highly disabling migraine subtype, affects nearly 2% of the general population. Understanding migraine chronification is vital for developing better treatment and prevention strategies. An important factor in the chronification of migraine is the overuse of acute headache medication. However, the mechanisms behind the transformation of episodic migraine to chronic migraine and vice
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Epigenetics of the far northern Yakutian population Clin. Epigenet. (IF 5.7) Pub Date : 2023-12-06 Alena Kalyakulina, Igor Yusipov, Elena Kondakova, Maria Giulia Bacalini, Cristina Giuliani, Tatiana Sivtseva, Sergey Semenov, Artem Ksenofontov, Maria Nikolaeva, Elza Khusnutdinova, Raisa Zakharova, Maria Vedunova, Claudio Franceschi, Mikhail Ivanchenko
Yakuts are one of the indigenous populations of the subarctic and arctic territories of Siberia characterized by a continental subarctic climate with severe winters, with the regular January average temperature in the regional capital city of Yakutsk dipping below − 40 °C. The epigenetic mechanisms of adaptation to such ecologies and environments and, in particular, epigenetic age acceleration in the
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DNA methylation profiles reveal sex-specific associations between gestational exposure to ambient air pollution and placenta cell-type composition in the PRISM cohort study Clin. Epigenet. (IF 5.7) Pub Date : 2023-12-01 Hachem Saddiki, Xueying Zhang, Elena Colicino, Ander Wilson, Itai Kloog, Robert O. Wright, Rosalind J. Wright, Corina Lesseur
Gestational exposure to ambient air pollution has been associated with adverse health outcomes for mothers and newborns. The placenta is a central regulator of the in utero environment that orchestrates development and postnatal life via fetal programming. Ambient air pollution contaminants can reach the placenta and have been shown to alter bulk placental tissue DNA methylation patterns. Yet the effect
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EZH2 K63-polyubiquitination affecting migration in extranodal natural killer/T-cell lymphoma Clin. Epigenet. (IF 5.7) Pub Date : 2023-11-29 Boheng Li, Qidi Zhou, Qin Wan, Xuan Qiao, Shangying Chen, Jianbiao Zhou, Zhijun Wuxiao, Lei Luo, Siok-Bian Ng, Jieping Li, Wee-Joo Chng
Overexpressed EZH2 is oncogenically involved in the pathogenesis of different cancerous contexts including extranodal natural killer/T cell lymphoma (ENKTL). However, the underlying mechanisms of EZH2 upregulation have not been fully clarified and it is still difficult to target EZH2 in ENKTL. Current study identifies an E3 ligase TRIP12 that triggers K63-linked polyubiquitination of EZH2 in ENKTL
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Epigenetic age acceleration in surviving versus deceased COVID-19 patients with acute respiratory distress syndrome following hospitalization Clin. Epigenet. (IF 5.7) Pub Date : 2023-11-28 Yosra Bejaoui, Fathima Humaira Amanullah, Mohamad Saad, Sara Taleb, Martina Bradic, Andre Megarbane, Ali Ait Hssain, Charbel Abi Khalil, Nady El Hajj
Aging has been reported as a major risk factor for severe symptoms and higher mortality rates in COVID-19 patients. Molecular hallmarks such as epigenetic alterations and telomere attenuation reflect the biological process of aging. Epigenetic clocks have been shown to be valuable tools for measuring biological age in various tissues and samples. As such, these epigenetic clocks can determine accelerated
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Long-term decitabine/retinoic acid maintenance treatment in an elderly sAML patient with high-risk genetics Clin. Epigenet. (IF 5.7) Pub Date : 2023-11-28 Nora Rebeka Javorniczky, Olga Grishina, Inga Hund, Milena Pantic, Dietmar Pfeifer, Claudia Schmoor, Johanna Thomas, Justus Duyster, Heiko Becker, Michael Lübbert
Elderly patients with AML ineligible for induction have a dismal prognosis; hence disease stabilization is a primary treatment goal. This case of a 75-year-old patient with secondary AML receiving the combination of decitabine and ATRA (within the DECIDER trial, NCT00867672) demonstrates an above-average survival. The therapy administered over 52 cycles led to complete molecular and hematological remission
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A 2-decade bibliometric analysis of epigenetics of cardiovascular disease: from past to present Clin. Epigenet. (IF 5.7) Pub Date : 2023-11-25 Yukang Mao, Kun Zhao, Nannan Chen, Qiangqiang Fu, Yimeng Zhou, Chuiyu Kong, Peng Li, Chuanxi Yang
Cardiovascular disease (CVD) remains a major health killer worldwide, and the role of epigenetic regulation in CVD has been widely studied in recent decades. Herein, we perform a bibliometric study to decipher how research topics in this field have evolved during the past 2 decades. Publications on epigenetics in CVD produced during the period 2000–2022 were retrieved from the Web of Science Core Collection
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Targeting oncogenic TERT promoter variants by allele-specific epigenome editing Clin. Epigenet. (IF 5.7) Pub Date : 2023-11-22 Alexandra G. Kouroukli, Nivethika Rajaram, Pavel Bashtrykov, Helene Kretzmer, Reiner Siebert, Albert Jeltsch, Susanne Bens
Activation of dominant oncogenes by small or structural genomic alterations is a common driver mechanism in many cancers. Silencing of such dominantly activated oncogenic alleles, thus, is a promising strategy to treat cancer. Recently, allele-specific epigenome editing (ASEE) has been described as a means to reduce transcription of genes in an allele-specific manner. In cancer, specificity to an oncogenic
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Histone deacetylase 3 deletion in alveolar type 2 epithelial cells prevents bleomycin-induced pulmonary fibrosis Clin. Epigenet. (IF 5.7) Pub Date : 2023-11-11 Rui Xiong, Boxin Geng, Wenyang Jiang, Yong Hu, Zhaoyu Hu, Bo Hao, Ning Li, Qing Geng
Epithelial mesenchymal transformation (EMT) in alveolar type 2 epithelial cells (AT2) is closely associated with pulmonary fibrosis (PF). Histone deacetylase 3 (HDAC3) is an important enzyme that regulates protein stability by modulating the acetylation level of non-histones. Here, we aimed to explore the potential role and regulatory mechanisms associated with HDAC3 in PF. We quantified HDAC3 expression
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DNA methylation sites in early adulthood characterised by pubertal timing and development: a twin study Clin. Epigenet. (IF 5.7) Pub Date : 2023-11-10 Emir Sehovic, Stephanie M. Zellers, Markus K. Youssef, Aino Heikkinen, Jaakko Kaprio, Miina Ollikainen
Puberty is a highly heritable and variable trait, with environmental factors having a role in its eventual timing and development. Early and late pubertal onset are both associated with various diseases developing later in life, and epigenetic characterisation of pubertal timing and development could lead to important insights. Blood DNA methylation, reacting to both genotype and environment, has been
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Tazemetostat decreases β-catenin and CD13 protein expression in HEPG-2 and Hepatitis B virus-transfected HEPG-2 with decreased cell viability Clin. Epigenet. (IF 5.7) Pub Date : 2023-11-08 Mohamed N. Amin, Yousra M. El-Far, Mohammed El-Mowafy, Abdelaziz Elgaml
Hepatocellular carcinoma (HCC) is one of the global health concerns. Hepatitis B virus (HBV) is one of the major causes of HCC. Poor clinical outcome of HCC patients is attributed to a small population of cancer cells known as cancer stem cells (CSCs). In this work, we studied the effect of inhibiting the enhancer of zeste homologue 2 (EZH2), a histone methyltransferase known to be overexpressed in