Epigenomics最新文献

Aneurysms are serious vascular conditions characterized by persistent dilatation of the blood vessel lumen, which can lead to rupture and become life-threatening. Their pathogenesis is complex and involves multiple biological mechanisms, including extracellular matrix degradation, oxidative stress, inflammation, and apoptosis of vascular smooth muscle cells. Long non-coding RNAs (lncRNAs), typically exceeding 200 nucleotides, perform numerous regulatory functions, including modulation of gene expression at the epigenetic, transcriptional, and post-transcriptional levels. Under pathological conditions, lncRNA expression can be markedly altered. A growing body of evidence indicates that lncRNAs play a key role in regulating cellular processes such as inflammation, apoptosis, and vascular remodeling, all of which are crucial to aneurysm development and progression. This review summarizes current knowledge on the involvement of lncRNAs in aneurysm pathophysiology and highlights recent research on their impact on vascular wall degradation, inflammatory responses, and smooth muscle cell survival. A literature review was conducted through a systematic search of PubMed, Scopus, and Web of Science using keywords related to lncRNAs and biological processes relevant to aneurysm development.

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy requiring improved early diagnosis and prognostic assessment. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, have emerged as promising biomarkers for ESCC. We conducted a comprehensive literature search in PubMed for studies published up to 2025. While miRNA profiles in ESCC tissues show significant associations with lymphatic dissemination, tumor progression, and patient survival, clinical translation remains limited by issues of sensitivity, specificity, and standardization. This review summarizes current knowledge on miRNA expression in ESCC, focusing on lymphatic dissemination and prognostic implications. We also explore circulating miRNAs as minimally invasive tools for early detection and treatment monitoring. By integrating recent findings, this article provides a critical overview of miRNA-based biomarkers to improve early diagnostic accuracy and therapeutic decision-making in ESCC.

Aims: To examine the relationship between DNA methylation of NR3C1 exon 1F and HSD11B2 promoters and neurodevelopment, and oral feeding skills in preterm infants.

Design: A longitudinal prospective cohort study was conducted.

Methods: Data from 61 preterm infants who were born between 26 to 34 weeks gestational age without major comorbidities were analyzed. DNA methylation was evaluated from buccal samples. Neurodevelopment and oral feeding skills were evaluated using the Neurobehavioral Assessment of the Preterm Infants and the Early Feeding Skills Assessment, respectively.

Results: Increased methylation at specific cytosine-guanine (CpG) dinucleotide sites within NR3C1 exon 1F and HSD11B2 promoters was associated with suboptimal neurodevelopmental and oral feeding outcomes, potentially reflecting heightened sensitivity to early life stress in the NICU. Conversely, certain methylation changes appear to be adaptive, promoting consistent suck-breathe coordination, or optimal behavioral and cardiorespiratory stability during oral feeding.

Conclusion: The study highlights the complex relationship between DNA methylation of NR3C1 exon 1F and HSD11B2 promoters and neurodevelopment, and oral feeding skills in preterm infants.

Implications for the profession and/or patient care: Findings emphasize the need for continued research into epigenetic mechanisms underlying neonatal adaptation and stress regulation, with potential implications for targeted epigenetic interventions to support optimal neurodevelopment and oral feeding skills.

Aim: This study aimed to clarify the mechanisms of E2F transcription factor 1 (E2F1) in the Cholesterol (CHOL) synthesis of Prostate cancer (PCa).

Methods: CHOL component content was detected using a commercial test kit. The interaction between E2F1 and staphylococcal nuclease domain-containing protein 1 (SND1) promoter was confirmed employing dual luciferase and chromatin immunoprecipitation assay. RNA immunoprecipitation and RNA pull-down analysis were utilized to validate the interaction between SND1 and ATP citrate lyase (ACLY) mRNA. A xenograft tumor model was used to confirm these mechanisms in vivo.

Results: E2F1, SND1, ACLY protein levels, along with CHOL concentrations, were up-regulated in human PCa tumor tissues. E2F1 enhanced cell proliferation, invasion, and CHOL synthesis in PCa cells. E2F1 could transcriptionally activate SND1, which subsequently bound to ACLY mRNA, stabilizing its expression. E2F1 induced CHOL synthesis via the enhancement of SND1/ACLY axis. E2F1 promoted CHOL synthesis and PCa tumor growth in vivo.

Conclusion: E2F1 enhanced cell proliferation, invasion, and tumor growth by enhancing CHOL synthesis via the SND1/ACLY axis in PCa models.

Background: Sarcopenic obesity (SO), defined as the coexistence of excess fat mass and low muscle mass/function, has been linked to adverse outcomes. Epigenetic alterations are central hallmarks of aging. Evaluating how obesity, sarcopenia, and SO are related to epigenetic aging biomarkers may provide insights into cellular aging and disease risk.

Methods: In this cross-sectional study, 30 older women were classified into the control, obesity, sarcopenia, and SO groups and underwent anthropometry measurements, body composition analysis, and handgrip strength. Blood DNA methylation (DNAm) biomarkers were used to estimate eight epigenetic clocks (Horvath, Hannum, DNAmTL, PhenoAge, GrimAge, GrimAge2, Zhang, and FitAge) and to calculate intrinsic and extrinsic epigenetic age acceleration (IEAA and EEAA). Associations were tested with Bayesian linear and quantile regressions, adjusted for age and HOMA-IR.

Results: SO was associated with higher EEAA, DNAmFitAge, and Hannum clock estimates, and shorter DNAmTL in both models. Obesity showed positive associations with these clocks in adjusted models and higher quantiles.

Conclusions: SO is associated with accelerated aging and shorter DNAmTL. Obesity contributes to biological aging, whereas sarcopenia without obesity does not. These findings suggest that excess adiposity combined with low muscle mass may worsen age-related decline, although the small sample size should be considered.

Introduction: Paternal biology before conception can influence offspring health beyond DNA sequence inheritance. Paternal exercise is a modifiable exposure that can remodel the male germline epigenome through DNA methylation, histone modifications, and small non-coding RNAs, potentially affecting offspring development and metabolism.

Methods: This systematic review searched PubMed/MEDLINE, Scopus, Web of Science, LILACS, and EMBASE without year restrictions. Experimental animal studies were eligible if sires exercised before conception and reported sperm or offspring epigenetic outcomes alongside molecular or phenotypic measures. Study selection followed predefined criteria.

Results: Of 14,409 records identified, 7836 duplicates were removed, and 6573 records were screened. Six studies met the inclusion criteria. Across treadmill and voluntary running paradigms, paternal exercise was associated with reduced offspring hippocampal DNA methylation, altered sperm small RNAs, decreased sperm H3K9 dimethylation, lower placental inflammatory mRNA expression, and improved offspring outcomes, including spatial learning, anxiety-like behavior, endurance, mitochondrial respiration, glucose tolerance, and insulin sensitivity.

Conclusion: Paternal exercise before conception remodels the male germline and is associated with beneficial metabolic, mitochondrial, and behavioral adaptations in offspring through epigenetic mechanisms, supporting its potential relevance for intergenerational health.

Protocol registration: https://www.crd.york.ac.uk/prospero identifier is CRD420251141579.

Objective: To investigate the genome-wide methylation changes in gallbladder tissues during gallstone formation, as well as alterations in key signaling pathways and associated gene expression.

Methods: A combined methylation and transcriptomic analysis was performed on gallbladder tissues from gallstone model mice and normal control mice using reduced representation bisulfite sequencing (RRBS) and RNA high-throughput sequencing. Key candidate genes were validated using qRT-PCR, Western blotting, and immunohistochemistry. Cross-species validation was conducted using human gallbladder transcriptomic data from GEO datasets.

Results: Integrated RRBS and RNA-seq analysis revealed that abnormal DNA methylation may contribute to gallstone formation by dysregulating gene expression in pathways associated with gallbladder dysfunction. A total of 97 differentially methylated and expressed genes exhibiting significant inverse correlations between methylation and expression levels were identified. The top six genes with the strongest correlations were experimentally validated. Analysis of human gallstone samples identified partial overlapping differentially expressed genes with the mouse model.

Conclusion: This study demonstrates the potential roles of DNA methylation and gene expression changes in gallbladder tissue during the formation of gallstones. These findings provide a new perspective for further understanding the causes of gallstones and searching for possible clinical therapies.

Aims: Mitochondrial DNA copy number (mtDNA-CN) is associated with several age-related chronic diseases and is a predictor of all-cause mortality. Here, we examine site-specific differential nuclear DNA (nDNA) methylation and differential gene expression resulting from in vitro reduction of mtDNA-CN to uncover shared genes and biological pathways mediating the effect of mtDNA-CN on disease.

Materials and methods: Epigenome and transcriptome profiles were generated for three independent human embryonic kidney (HEK293T) cell lines harboring a mitochondrial transcription factor A (TFAM) knockout generated via CRISPR-Cas9, and matched control lines.

Results: We identified 2924 differentially methylated sites, 67 differentially methylated regions, and 102 differentially expressed genes associated with mtDNA-CN. Integrated analysis uncovered 24 Gene-CpG pairs. GABA_A receptor genes and related pathways, the neuroactive ligand signaling pathway, ABCD1/2 gene activity, and cell signaling processes were overrepresented, providing insight into the underlying biological mechanisms facilitating these associations. We also report evidence implicating chromatin state regulatory mechanisms as modulators of mtDNA-CN effect on gene expression.

Conclusions: We demonstrate that mitochondrial DNA variation signals to the nuclear DNA epigenome and transcriptome and may lead to nuclear remodeling relevant to development, aging, and complex disease.

Background: Chronic social defeat stress (CSDS) is a validated animal model for depression that produces sustained behavioral and transcriptional changes in the brain, notably the nucleus accumbens (nAcc).

Research design and methods: We used genome-wide analysis of cytosine methylation patterns in mouse nAcc following CSDS to identify candidate epigenetic mechanisms.

Results: CSDS produced extensive differential methylation, increasing CG hypermethylation compared to control conditions; non-CG methylation showed the opposite trend. Highly differentially methylated (DM) regions included several genes implicated in behavioral effects of CSDS, including estrogen receptor alpha (Esr1).

Conclusions: Analysis of DM sites within gene bodies revealed ß-catenin as a hub gene of a network including the ß-catenin-related WNT/frizzled signaling pathway. Analysis of DM sites upstream of transcription start sites revealed a gene network with the Tcf4 transcription factor as a hub. Genes DM within the gene body were enriched for synaptic function and primarily expressed in D1+ and D2+ medium spiny neurons, which, like the WNT/ß-catenin pathway, are estrogen sensitive and implicated in the behavioral effects of CSDS. We found significant overlap between DM genes associated with CSDS and those associated with major depressive disorder in genome-wide association studies, suggesting that effects on DNA methylation are implicated in the molecular pathways that link chronic stress to depression.