PETScan: Score-Based Genome-Wide Association Analysis of RNA-Seq and ATAC-Seq Data DOI Creative Commons
Yajing Hao, Tal Kafri, Fei Zou

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Abstract High-dimensional sequencing data, such as RNA-Seq for gene expression and ATAC-Seq chromatin accessibility, are widely used in studying systems biology. Accessible allows transcription factors regulatory elements to bind DNA, thereby regulating through the activation or repression of target genes. The association analysis data provides insights into mechanisms. Most existing analytic tools exclusively focus on cis-associations, despite being able physically interact with distant Furthermore, conventional approaches often utilize Pearson Spearman correlations, which ignore count-based nature data. To address these limitations, we introduce PETScan , a computationally efficient genome-wide PE ak- T ranscript Sc ore-based an alysis, utilizing negative binomial models better accommodate We leverage score tests matrix calculations improved computational efficiency, combine empirical permutation method genomic control ensure valid p-value studies limited sample sizes. In real-world datasets, achieved three orders magnitude faster than Wald tests, while identifying similar significant gene-peak pairs. R package is available GitHub at https://github.com/yajing-hao/PETScan .

Language: Английский

Oxidative-Stress-Mediated Epigenetic Dysregulation in Spermatogenesis: Implications for Male Infertility and Offspring Health DOI Open Access
Aris Kaltsas,

Eleftheria Markou,

Maria-Anna Kyrgiafini

et al.

Genes, Journal Year: 2025, Volume and Issue: 16(1), P. 93 - 93

Published: Jan. 17, 2025

Male reproductive health is governed by an intricate interplay of genetic, epigenetic, and environmental factors. Epigenetic mechanisms—encompassing DNA methylation, histone modifications, non-coding RNA activity—are crucial both for spermatogenesis sperm maturation. However, oxidative stress, driven excessive reactive oxygen species, disrupts these processes, leading to impaired function male infertility. This disruption extends epigenetic resulting in abnormal gene expression chromatin remodeling that compromise genomic integrity fertilization potential. Importantly, oxidative-stress-induced alterations can be inherited, affecting the fertility offspring future generations. review investigates how stress influences regulation reproduction modifying RNAs, ultimately compromising spermatogenesis. Additionally, it discusses transgenerational implications disruptions their potential role hereditary infertility disease predisposition. Understanding mechanisms vital developing therapeutic strategies mitigate damage restore homeostasis germline. By integrating insights from molecular, clinical, research, this work emphasizes need targeted interventions enhance prevent adverse outcomes progeny. Furthermore, elucidating dose–response relationships between changes remains a critical research priority, informing personalized diagnostics interventions. In context, studies should adopt standardized markers damage, robust clinical trials, multi-omic approaches capture complexity Such rigorous investigations will reduce risk disorders optimize outcomes.

Language: Английский

Citations

3
Epigenetics in autoimmune diseases: Unraveling the hidden regulators of immune dysregulation DOI Creative Commons
Giacomo Bagni, Edoardo Biancalana,

Emanuele Chiara

et al.

Autoimmunity Reviews, Journal Year: 2025, Volume and Issue: 24(6), P. 103784 - 103784

Published: March 3, 2025

Autoimmune diseases result from complex interactions between genetic and environmental factors. Recent advances in epigenetic research shed light on the intricate regulatory mechanisms that contribute to development progression of such conditions. The present review aims explore role modifications, including DNA methylation, histone non-coding RNAs, context autoimmune diseases. We discuss current understanding alterations associated with various disorders, their impact immune cell function, potential as innovative therapeutic targets. Additionally, we highlight main future directions field epigenetics autoimmunity.

Language: Английский

Citations

2
Exploring viral mimicry combined with epigenetics and tumor immunity: new perspectives in cancer therapy DOI Creative Commons
Ruirui Wang, Xin Dong,

Xiongjian Zhang

et al.

International Journal of Biological Sciences, Journal Year: 2025, Volume and Issue: 21(3), P. 958 - 973

Published: Jan. 6, 2025

Viral mimicry refers to an active antiviral response triggered by the activation of endogenous retroviruses (ERVs), usually manifested formation double-stranded RNA (dsRNA) and cellular interferon response, which activates immune system produces anti-tumor effects. Epigenetic studies have shown that epigenetic modifications (e.g. DNA methylation, histone modifications, etc.) play a crucial role in tumorigenesis, progression, treatment resistance. Particularly, alterations methylation may be closely associated with suppression ERVs expression, demethylation restore activity thus strengthen tumor response. Therefore, we propose viral can induce responses microenvironment activating expression ERVs, key regulatory this process. In paper, review intersection mimicry, epigenetics immunotherapy, explore possible interactions synergistic effects among three, aiming provide new theoretical basis potential strategies for cancer immunotherapy.

Language: Английский

Citations

1
Bridging epigenomics and tumor immunometabolism: molecular mechanisms and therapeutic implications DOI Creative Commons
Xiaowen Xie, Weici Liu, Zhiyuan Yuan

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 8, 2025

Epigenomic modifications—such as DNA methylation, histone acetylation, and methylation—and their implications in tumorigenesis, progression, treatment have emerged a pivotal field cancer research. Tumors undergo metabolic reprogramming to sustain proliferation metastasis nutrient-deficient conditions, while suppressing anti-tumor immunity the tumor microenvironment (TME). Concurrently, immune cells within immunosuppressive TME adaptations, leading alterations function. The complicated interplay between metabolites epigenomic modulation has spotlighted significance of regulation immunometabolism. In this review, characteristics modification associated with tumors are systematically summarized alongside regulatory roles Classical emerging approaches delineated broaden boundaries research on crosstalk immunometabolism epigenomics. Furthermore, we discuss potential therapeutic strategies that target modulate modifications, highlighting burgeoning synergy therapies immunotherapy promising avenue for treatment.

Language: Английский

Citations

1
Current Research in Drug-Free Cancer Therapies DOI Creative Commons

Akshaya Andavar,

Varsha Rajesh Bhagavathi,

J Cousin

et al.

Bioengineering, Journal Year: 2025, Volume and Issue: 12(4), P. 341 - 341

Published: March 26, 2025

Cancer treatment has historically depended on conventional methods like chemotherapy, radiation, and surgery; however, these strategies frequently present considerable limitations, including toxicity, resistance, negative impacts healthy tissues. In addressing challenges, drug-free cancer therapies have developed as viable alternatives, utilizing advanced physical biological to specifically target tumor cells while reducing damage normal This review examines several strategies, such high-intensity focused energy beams, nanosecond pulsed electric fields, photothermal therapy well the use of inorganic nanoparticles promote selective apoptosis. We also investigate significance targeting microenvironment, precision medicine, immunotherapy in progression personalized therapies. Although approaches demonstrate significant promise, challenges scalability, safety, regulatory obstacles must be resolved for clinical application. paper presents an overview current research therapies, emphasizing recent advancements, underlying scientific principles, steps required implementation.

Language: Английский

Citations

1
The class-IIa HDAC inhibitor TMP269 promotes BMP-Smad signalling and is neuroprotective in in vitro and in vivo 6-hydroxydopamine models of Parkinson’s disease. DOI Creative Commons
Alexander T. O’Mahony, Martina Mazzocchi,

Alex Morris

et al.

Neuropharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 110319 - 110319

Published: Jan. 1, 2025

Language: Английский

Citations

1
Transcription Machinery Anchors ecDNAs to Mitotic Chromosomes for Segregation DOI Creative Commons
Ying Xie, Jun Yi Stanley Lim, Wenyue Liu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Abstract Extrachromosomal DNA (ecDNA) is a prevalent driver of cancer, whose random segregation promotes aggressive tumors. Acentric ecDNAs attach to chromosomes during mitosis for segregation. However, the molecular mechanism governing ecDNA-chromosome mitotic interactions remains poorly understood. This study shows that histone 3 lysine 27 acetylation (H3K27ac)-marked chromatin mitosis. H3K27ac depletion resulted in ecDNA detachment from chromosomes. Diverse bromodomain proteins, which are known readers H3K27ac, stabilize ecDNAs’ interaction, exhibiting context-dependent and mutually complementary roles. Furthermore, disruptions Mediator complex RNA polymerase II transcription activity both dissociate chromosomes, suggesting machinery mediates Mis-segregated were expelled into cytosol degraded, leading diminished oncogene expression reversal therapy resistance. Our research provides new insights interplay between acentric inheritance offering novel avenue disrupting ecDNA-driven oncogenesis.

Language: Английский

Citations

0
Epigenetic Regulation of Stromal and Immune Cells and Therapeutic Targets in the Tumor Microenvironment DOI Creative Commons
Kang Liu, Yue Li, Minmin Shen

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 71 - 71

Published: Jan. 6, 2025

The tumor microenvironment (TME) plays a pivotal role in neoplastic initiation and progression. Epigenetic machinery, governing the expression of core oncogenes suppressor genes transformed cells, significantly contributes to development at both primary distant sites. Recent studies have illuminated how epigenetic mechanisms integrate external cues downstream signals, altering phenotype stromal cells immune cells. This remolds area surrounding ultimately fostering an immunosuppressive microenvironment. Therefore, correcting TME by targeting modifications holds substantial promise for cancer treatment. review synthesizes recent research that elucidates impact specific regulations-ranging from DNA methylation histone chromatin remodeling-on within TME. Notably, we highlight their functional roles either promoting or restricting We also discuss potential applications agents treatment, envisaging ability normalize ecosystem. aims assist researchers understanding dynamic interplay between epigenetics TME, paving way better therapy.

Language: Английский

Citations

0
c-FLIP/Ku70 complex; A potential molecular target for apoptosis induction in hepatocellular carcinoma DOI

Yasamin Haghir-Sharif-Zamini,

Arezoo Khosravi, Moustapha Hassan

et al.

Archives of Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: unknown, P. 110306 - 110306

Published: Jan. 1, 2025

Language: Английский

Citations

0
The Role of the DNA Methyltransferase Family and the Therapeutic Potential of DNMT Inhibitors in Tumor Treatment DOI Creative Commons
Dae Joong Kim

Current Oncology, Journal Year: 2025, Volume and Issue: 32(2), P. 88 - 88

Published: Feb. 5, 2025

Members of the DNA methyltransferase (DNMT) family have been recognized as major epigenetic regulators altered gene expression during tumor development. They establish and maintain methylation CpG island promoter non-CpG region genome. The abnormal status suppressor genes (TSGs) has associated with tumorigenesis, leading to genomic instability, improper silence, immune evasion. DNMT1 helps preserve patterns replication, whereas DNMT3 is responsible for de novo methylation, creating new patterns. Altered significantly supports growth by changing FDA-approved DNMT inhibitors reverse hypermethylation-induced repression improve therapeutic outcomes cancer. Recent studies indicate that combining chemotherapies immunotherapies can synergistic effects, especially in aggressive metastatic tumors. Improving treatment schedules, increasing isoform specificity, reducing toxicity, utilizing genome-wide analyses CRISPR-based editing create personalized therapies tailored individual patient needs are promising strategies enhancing outcomes. This review discusses interaction between DNMT1, its binding partners, connection tumors, how these processes contribute development, inhibitors’ advancements pharmacological properties.

Language: Английский

Citations

0