Search Results (173)

Objective: Patients with systemic lupus erythematosus (SLE) exhibit elevated malignancy risk, with increased bladder cancer incidence. This study integrated Mendelian randomization (MR) with single-cell sequencing (scRNA-seq) to nominate exploratory prioritized candidate genes in SLE–bladder cancer comorbidity and their T cell regulatory roles. Methods: Single-cell datasets for SLE (GSE266852) and bladder cancer (GSE222315) were retrieved from GEO. Quality control, clustering, and annotation were performed using Seurat. T cell differentially expressed genes were intersected for bidirectional two-sample MR using IEU Open GWAS statistics. Heterogeneity, pleiotropy, and sensitivity analyses assessed robustness. GeneMANIA, miRNA databases, and CTD were used for network and functional analyses. Wilcoxon tests and Monocle 2 were used to characterize expression and T cell differentiation trajectories. Results: Cross-disease intersection nominated 1010 candidate genes. In an exploratory MR screen (uncorrected p < 0.05), four candidate genes were nominated (GBP3, LMAN1, SLC40A1, MIS18BP1); none survived FDR correction in both directions. At the uncorrected threshold, LMAN1 showed a shared risk direction (OR > 1) and MIS18BP1 a protective direction (OR < 1). Both showed significant T cell differential expression (p < 0.001) and elevated late differentiation expression. LMAN1 was involved in COPII vesicle transport; MIS18BP1 in CENP-A chromatin assembly. Twenty high-confidence miRNAs targeted each gene. CTD indicated liver injury associations and cisplatin/cyclosporine interactions. Conclusions: LMAN1 and MIS18BP1 are proposed as hypothesis-generating exploratory candidate genes in SLE–bladder cancer comorbidity, potentially involved in immune dysregulation through T cell terminal differentiation modulation. This study provides preliminary evidence suggestive of autoimmune–malignancy comorbidity mechanisms. Full article

In contrast to foreign nucleic acids, some of our own endogenously synthesized nucleic acids may become immunologically active without being considered “foreign”. For example, abnormalities in chromatin organization, transcription termination, ribonucleic acid (RNA) splicing, and RNA editing, together with damage to mitochondrial integrity, may render normally functional deoxyribonucleic acid (DNA) and RNA persistently available and aberrantly structured ligands for innate immunity. Z-DNA-binding protein 1 (ZBP1), recently identified as an important component of this innate immune system, recognizes both left-handed DNA (Z-DNA) and left-handed RNA (Z-RNA) using its tandem Z-alpha (Zα) domains and couples recognition of these conformational states to receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-, receptor-interacting serine/threonine-protein kinase 3 (RIPK3)-, and mixed-lineage kinase domain-like pseudokinase (MLKL)-dependent inflammatory and cell-death pathways. More recent studies have also shown that ZBP1 plays a role in recognizing damaged self-nucleic acids associated with tauopathies, Alzheimer’s disease (AD), traumatic brain injury (TBI), and amyloid-associated neuroinflammation. The nucleic-acid forms associated with these conditions include transposable-element activation, extended repeat-containing transcripts, RNA–RNA duplexes or RNA:DNA hybrids, oxidized mitochondrial DNA (mtDNA), and intercellularly transferred nucleic acids, all of which may exhibit substrate structures compatible with Z-form formation. Signaling by ZBP1 does not occur simply based upon nucleic-acid abundance; rather, signaling occurs after prolonged exposure to a nucleic acid when it persists in a structurally competent state, sufficient receptors are present to bind its exposed regions, the receptor proteoforms are competent to participate in signaling, receptor-interacting protein homotypic interaction motif (RHIM)-dependent assembly occurs, and the appropriate adaptor molecules are present. Furthermore, the identity of the cell type expressing ZBP1 determines whether the response produces RIPK3–MLKL-dependent neuronal injury, microglia-mediated inflammation, apoptosis, or mixed cell death. Finally, competition with adenosine deaminase acting on RNA 1 (ADAR1), melanoma differentiation-associated protein 5 (MDA5), double-stranded RNA-dependent protein kinase (PKR), the cyclic guanosine monophosphate–adenosine monophosphate synthase–stimulator of interferon genes (cGAS–STING) pathway, and other nucleic-acid-sensing proteins divides the available pool of endogenous nucleic acids among the outcomes of immune tolerance, type I interferon (IFN-I) signaling, translational inhibition, neuroinflammation, and necroptosis. Full article

The cohesin complex is a highly conserved, ring-shaped protein assembly that plays fundamental roles in chromosome biology. Originally identified as the molecular glue that holds sister chromatids together from DNA replication until cell division, cohesin has since been recognized as a pleiotropic regulator of genome organization, gene expression, DNA repair, and cell fate determination. In embryonic stem cells (ESCs), cohesin’s functions extend beyond canonical sister chromatid cohesion to include the maintenance of three-dimensional (3D) chromatin architecture through DNA loop extrusion, regulation of pluripotency-associated transcriptional programs, and facilitation of homologous recombination-mediated DNA repair during the prolonged S phase. Recent discoveries have revealed that meiosis-specific cohesin components, particularly the α-kleisin subunit REC8 and its interacting partner STAG3, are expressed and functionally active in mitotic ESC chromosomes, where they contribute to chromosomal organization and sister chromatid cohesion in concert with mitotic RAD21-containing cohesin. Furthermore, the interplay between cohesin and condensin complexes at shared genomic binding sites has emerged as a critical determinant of chromosome topology, with cohesin depletion leading to aberrant condensin accumulation and chromosome hypercompaction. Importantly, perturbations in cohesin function not only impair ESC self-renewal but also direct lineage-specific differentiation, linking cohesin to stem cell fate determination. Germline mutations in cohesin and its regulators underlie a spectrum of developmental disorders termed cohesinopathies, while somatic mutations are frequently observed in various cancers. This review provides a comprehensive overview of the diverse roles of cohesin in chromosome structure, cell cycle regulation, and stem cell biology, with particular emphasis on recent findings in ESCs that illuminate the complex interplay between mitotic and meiotic cohesin complexes. Full article

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of clinically aggressive mature T-cell and natural killer (NK)-cell neoplasms that account for approximately 10–15% of all non-Hodgkin lymphomas in Western countries . The most common subtypes include extranodal NK/T-cell lymphoma (ENKTL), nodal T-follicular helper cell lymphomas, peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), anaplastic large cell lymphoma (ALK-positive and ALK-negative), and T-cell lymphoblastic lymphoma. Non-coding RNAs (ncRNAs) constitute the majority of the human transcriptome and play critical roles in regulating gene expression, cellular proliferation, differentiation, migration, and apoptosis. Among these, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) have emerged as key regulators of lymphomagenesis and disease progression in PTCLs. These molecules modulate diverse oncogenic pathways through chromatin remodeling, transcriptional regulation, competing endogenous RNA activity, and interactions with RNA-binding proteins, thereby influencing proliferation, immune evasion, treatment resistance, and clinical outcomes. Representative examples include the lncRNA TCLlnc1, which promotes PTCL progression through activation of transforming growth factor-β (TGF-β) signaling, and the circRNAs circKIF4A, circADARB1, and circ-LAMP1, which regulate miRNA-dependent signaling networks involving PDK1/BCL11A, STAT3, and DDR2, respectively. In this review, we summarize the current understanding of the biological and clinical roles of lncRNAs and circRNAs in PTCL and related T-cell and NK-cell neoplasms and highlight their potential as diagnostic and prognostic biomarkers as well as therapeutic targets. We also discuss recent advances and future directions for integrating ncRNA-based approaches into precision medicine for T-cell lymphoma. Full article

Glioblastoma (GBM) exhibits marked sex differences in incidence, outcome, and molecular regulation, yet the mechanisms underlying these disparities remain poorly defined. ZEB1 is a neurodevelopmental transcription factor implicated in GBM progression and cellular plasticity, but its prognostic and functional relevance may differ by sex. Here, we analyzed TCGA-GBM transcriptomic and clinical data to assess the relationship between ZEB1 expression, patient sex, and survival and to identify sex-specific transcriptional programs associated with ZEB1. Patients were stratified by ZEB1 expression and sex, followed by differential expression analysis, functional enrichment, and survival modeling. High ZEB1 expression was associated with improved overall survival in female patients but not in male patients. Sex-stratified transcriptomic analysis revealed distinct ZEB1-associated gene expression signatures, with enrichment of chromatin-modifying and demethylase-related pathways among male–female comparisons. Candidate Y-linked epigenetic regulators, including KDM5D and UTY, were differentially expressed in ZEB1-high male tumors. qPCR validation in male and female patient-derived GBM cell lines supported sex-dependent regulation of these candidates and showed that KDM5D and UTY expression was reduced following ZEB1 knockdown in male cells. Together, these findings identify a sex-dependent prognostic role for ZEB1 in GBM and suggest that ZEB1 interacts with sex-chromosome-linked epigenetic regulators to shape tumor transcriptional states. Full article

Triple-negative breast cancer (TNBC) remains a highly aggressive malignancy with limited therapeutic options and frequent resistance to platinum-based chemotherapy. Rosmarinic acid (RA), a naturally occurring polyphenol, has attracted considerable interest as a potential chemosensitising agent. This study investigated the anticancer activity and the underlying mechanisms of RA combined with cisplatin (CDDP) in 4T1 breast cancer cells while assessing the cytotoxic responses of non-cancerous HaCaT keratinocytes as a preliminary indicator of differential treatment sensitivity. Cytotoxicity was assessed using the MTT assay, followed by calculation of the Combination Index (CI), Drug Reduction Index (DRI), and Selectivity Index (SI). The generation of intracellular reactive oxygen species (ROS) was evaluated by DCFH-DA fluorescence imaging, and the functional contribution of oxidative stress was examined using N-acetyl-L-cysteine (NAC) rescue experiments. Apoptosis was analysed by Annexin V/PI flow cytometry, NucBlue nuclear staining, and Calcein-AM/propidium iodide (PI) Live/Dead fluorescence imaging. Three-dimensional (3D) tumour spheroids were used to assess treatment-induced alterations in spheroid morphology, morphometric parameters, viability based on adenosine triphosphate (ATP), and Live/Dead staining. The expression of genes related to apoptosis was determined by RT-qPCR, and potential molecular mechanisms were explored using the construction of protein–protein interaction (PPI) networks together with Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses. The combination of RA + CDDP exhibited strong synergistic cytotoxicity in 4T1 cells while demonstrating comparatively lower toxicity toward HaCaT keratinocytes. Combination treatment markedly increased intracellular ROS generation, whereas NAC significantly reduced ROS accumulation and partially restored cell viability, indicating that oxidative stress is a major but not exclusive mediator of cytotoxicity. Combined treatment significantly enhanced apoptotic cell death, increased chromatin condensation and membrane damage, upregulated the expression of Bax, Casp9, Cycs, and Trp53, and downregulated Bcl2, consistent with transcriptional regulation of intrinsic apoptotic signalling. In 3D tumour spheroids, the combination markedly reduced spheroid size, disrupted structural integrity, decreased ATP-based viability, and substantially increased tumour cell death compared to monotherapy. Bioinformatic analyses identified central genes related to apoptosis and cell survival and predicted significant enrichment of PI3K/Akt, p53, MAPK, and apoptosis signalling pathways. RA significantly potentiates the antitumor efficacy of CDDP through synergistic induction of ROS-associated apoptotic signalling while showing a more favourable cytotoxic response in 4T1 breast cancer cells than in non-cancerous HaCaT keratinocytes. The integrated findings from two-dimensional (2D) and 3D models, NAC rescue experiments, molecular analyses, and bioinformatics collectively support the potential of RA as a promising chemosensitising adjuvant for CDDP-based breast cancer therapy and warrant further validation in preclinical in vivo models. Full article

Acute myeloid leukaemia (AML) is a therapeutically challenging malignancy driven by the self-renewal, quiescence, and therapy resistance of leukaemic stem cells (LSCs). CDK8, a kinase component of the Mediator complex, regulates oncogenic transcription, and the selective CDK8/CDK19 inhibitor RVU120 (Romaciclib) targets AML cells with CD34⁺/pSTAT5-high LSC-like characteristics; however, the epigenetic and transcriptional consequences of CDK8 blockade and actionable combinatorial strategies remain incompletely defined. Using the TEX cell line, an LSC-enriched surrogate model, we performed time-resolved RNA-seq, whole-proteome and phosphoproteomics mass spectrometry (MS), and CUT&Tag chromatin profiling following treatment with RVU120 and CCT251921. CDK8 protein–protein interactions were mapped by co-immunoprecipitation MS across five AML models, and synergy with Pelabresib (BET inhibitor) or CB6644 (RUVBL1/2 inhibitor) was assessed by high-content screening in three cell lines and three patient-derived xenograft (PDX) models. Both inhibitors suppressed STAT5 phosphorylation, induced loss of the CD34⁺/CD38⁻ LSC-enriched phenotype, and drove erythromegakaryocytic differentiation. Transcriptomic and proteomic responses were concordant, and CDK8 inhibition triggered widespread enhancer activation with redistribution of RNAP2, BRD3, and NFRKB. CDK8 combined with Pelabresib acted synergistically in MOLM-16 cells and two of three PDX models. These findings identify CDK8 as a transcriptional node of LSC-associated programs and provide a mechanistic rationale for combined CDK8-BET inhibition in molecularly defined AML subsets, which will require validation in functional LSC assays and primary specimens. Full article

Bumped kinase inhibitor 1708 (BKI-1708), previously demonstrated to target apicomplexan kinases and CDPK1 and MAPKL1, exhibits remarkable activity against Toxoplasma gondii infection both in vitro and in vivo. Notably, BKI-1708 does not affect the viability of mammalian cells. Upon exposure to BKI-1708, T. gondii tachyzoites form large multinucleated complexes named baryzoites and remain trapped within host cells. In this study, proteins binding to BKI-1708 were identified in soluble extracts of T. gondii ME49 tachyzoites and human foreskin fibroblasts (HFF) using differential affinity chromatography coupled to mass spectrometry (DAC-MS). Beyond kinases, secondary interactions in T. gondii involved the binding of proteins associated with cell division, cytoskeleton, vesicular trafficking, secretory organelles, and transcriptional and translational regulators. In non-infected HFFs, BKI-1708 interactors included cytoskeletal regulators along with multiple RNA/DNA-binding proteins. Upon infection, this profile shifted, with cytoskeletal components no longer detected, while nucleic acid-binding proteins remained present, consistent with infection-induced chromatin and transcriptional remodeling. These results suggest that multi-target interference could contribute to the impaired cytokinesis and the formation of multinucleated baryzoites, aligning with the concept that antiprotozoal drugs exert efficacy through coordinated perturbation of multiple cellular processes rather than a single dominant target. Full article

Intramuscular fat content is a key determinant of pork quality, influencing traits such as tenderness, juiciness, and flavor. However, the molecular mechanisms regulating intramuscular fat deposition in indigenous pig breeds remain incompletely understood. This study aimed to identify genes and regulatory mechanisms associated with intramuscular fat accumulation in Hezuo pigs. Longissimus dorsi muscle samples from Hezuo pigs with extreme high and low intramuscular fat contents were subjected to chromatin accessibility profiling and transcriptome sequencing. Comparative analyses identified 2201 differentially accessible chromatin regions and 588 differentially expressed genes between the two groups. Functional enrichment analyses indicated that these genes were mainly involved in lipid metabolism, focal adhesion, extracellular matrix–receptor interaction, fatty acid metabolism, and adenosine monophosphate-activated protein kinase signaling. Integration of chromatin accessibility and gene expression datasets identified 92 co-regulated genes associated with intramuscular fat deposition, including MYLK3, PDGFC, PAK1, IGF1R, LAMA4, DIAPH1, SDC4, GADD45G, and RXRG. These findings reveal regulatory networks underlying intramuscular fat accumulation in Hezuo pigs and provide candidate genes and molecular resources for improving meat quality through genetic selection and breeding programs. Full article

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants associated with neurodevelopmental and neurodegenerative disorders. PCB 118 is one of the most abundant congeners and exerts neurotoxic effects, yet the molecular mechanisms underlying its impact on human neurons remain poorly understood. We investigated the molecular response of retinoic acid-differentiated, neuron-like SH-SY5Y cells exposed to 5 µM PCB 118 for 24 h, a concentration that did not affect cell viability. RNA sequencing identified 1239 differentially expressed genes. Functional enrichment and protein-protein interaction analyses identified upregulation of histone and chromatin structural genes, indicative of substantial chromatin remodeling. In parallel, a significant downregulation of genes involved in ribosome biogenesis and rRNA processing was observed, potentially indicating impairment of the protein synthesis machinery. These transcriptional changes point to a coordinated reprogramming of nuclear architecture and translational machinery, potentially compromising neuronal homeostasis. The modulation of proteostasis-related pathways further supports a mechanistic link between PCB 118 exposure and neuronal dysfunction. Our results provide a comprehensive transcriptional framework connecting PCB 118 to chromatin-mediated gene regulation and suppression of ribosome biogenesis in human neuron-like cells. This study offers mechanistic insights into how environmental PCB exposure may contribute to neurotoxicity and highlights molecular pathways potentially implicated in the development of neurodegenerative disorders. Full article

Among the transcriptional dependencies that sustain leukemic identity in acute myeloid leukemia (AML), the menin–KMT2A chromatin complex has emerged as a central regulatory node. The scaffold protein menin, encoded by MEN1, facilitates transcriptional activation of HOX and MEIS family genes during normal hematopoietic development. In AML, this physiologic and developmentally regulated role is co-opted to sustain constitutive HOX/MEIS-driven programs that block differentiation and maintain leukemic potential. Although dependency on menin is most clearly established in KMT2A-rearranged and NPM1-mutated AML, this vulnerability appears to arise from a shared transcriptional state characterized by persistent HOX activation rather than from any single genetic alteration. Pharmacologic disruption of the menin-KMT2A interaction collapses stemness-associated transcriptional networks, promotes myeloid differentiation, and attenuates leukemic self-renewal. Clinical activity observed with menin inhibitors provides translational validation of this dependency and establishes menin inhibition as a differentiation-based therapeutic strategy. In this review, we examine the molecular basis of menin-dependent transcriptional regulation in AML and its implications for therapeutic targeting with menin inhibitors and resistance to therapy. Full article

Uterine smooth muscle tumors (USMTs) represent a diverse group of neoplasms arising from the myometrium, ranging from benign uterine fibroids (leiomyomas) to highly aggressive uterine leiomyosarcoma. While genetic alterations contribute to tumor development, growing evidence highlights the crucial role of epigenetic regulation in shaping tumor behavior. Among these mechanisms, histone modification has emerged as a key regulator of chromatin structure and gene expression. Histone modifications, including acetylation, methylation, phosphorylation, ubiquitination, ADP-ribosylation, and SUMOylation, are dynamically controlled by epigenetic regulators known as writers, erasers, and readers, which collectively modulate transcriptional programs involved in cell proliferation, differentiation, and stress responses. Recent studies indicate that dysregulation of histone-modifying enzymes contributes to the pathogenesis of USMTs by altering chromatin accessibility and transcriptional networks. In uterine fibroids, histone modifications are associated with hormone-responsive signaling pathways, extracellular matrix deposition, and abnormal smooth muscle cell proliferation. In contrast, uterine leiomyosarcoma exhibits extensive epigenetic reprogramming characterized by aberrant histone acetylation and methylation patterns, dysregulated chromatin regulators, and activation of oncogenic signaling pathways that promote tumor aggressiveness and genomic instability. Importantly, histone modifications interact with other epigenetic mechanisms, including DNA methylation, non-coding RNA–mediated regulation, and RNA epitranscriptomics, forming complex networks that influence tumor initiation and progression. This narrative review summarizes current knowledge on histone modification pathways and their roles in USMT biology, highlighting the functions of histone-modifying enzymes, their interactions with other epigenetic mechanisms, and their impact on tumor development. In addition, this review discusses emerging therapeutic strategies targeting epigenetic regulators, including inhibitors of histone deacetylases, histone methyltransferases, and readers, as well as potential epigenetic biomarkers for diagnosis and prognosis. Finally, this review outlines future research directions, including multi-omics integration, and advanced epigenomic technologies, which may provide deeper insights into the epigenetic landscape of USMTs and facilitate the development of personalized therapeutic approaches. Full article

Background: Adipogenesis is governed by a complex interplay between transcriptional regulation and epigenetic remodeling. While many transcriptional pathways have been well characterized, less is known about how chromatin-level regulation shapes the timing of gene expression, particularly in large animal models such as pigs. In this study, we investigated histone modification patterns associated with four key adipogenic transcription factor genes—PPARG, GATA2, CEBPA, and CEBPB—in porcine mesenchymal stem cells (MSCs) undergoing adipogenic differentiation. Methods: Using RT-qPCR and ChIP-qPCR, we profiled gene transcription levels and epigenetic marks, including promoter- and exon-specific enrichment of the activating histone marks H3K9ac and H4K8ac, as well as the repressive mark H4K20me3, across six time points (day 0, 2, 4, 6, 8, and 10). Results: Although PPARG and GATA2 are located in close proximity on porcine chromosome 13, they exhibited distinct histone modification profiles. PPARG showed progressive promoter acetylation (H4K8ac) accompanied by transcriptional activation, whereas GATA2 displayed decreased exon acetylation (H3K9ac) associated with declining expression. In contrast, the H4K20me3 profile was similar for both genes, suggesting no direct association with their transcriptional activity. Interestingly, CEBPA (chromosome 6) and CEBPB (chromosome 17) exhibited temporally distinct histone modification patterns consistent with their roles in intermediate and early stages of adipogenic differentiation, respectively. Increased enrichment of the H3K9ac mark preceded the rise in transcript levels of the analyzed genes. Promoter regions showed higher enrichment of H4K8ac compared with exonic regions. A higher level of H4K20me3 was also observed for CEBPA and CEBPB than for PPARG and GATA2, which appeared to be more related to chromosomal localization than to direct transcriptional regulation. Conclusions: Together, these results reveal complex interactions between transcriptional dynamics and selected histone modifications that depend on both the gene analyzed and the stage of adipocyte differentiation. This study provides new insights into the epigenetic regulation of porcine adipogenesis and highlights chromatin context as an additional layer influencing transcriptional control. Full article

Long non-coding RNAs (lncRNAs) interact with chromatin and recruit epigenetic complexes to specific genomic loci, yet their relationship with super-enhancers (SEs), key regulatory elements frequently reprogrammed in cancer, remains unexplored. We developed an integrative pipeline that combines RNA–chromatin contact data (RNA-Chrom), histone modification–lncRNA expression correlation profiles (HiMoRNA peaks), and super-enhancer annotations (SEdb 3.0) to map lncRNA–SE regulatory axes. Applying this framework to SNHG1 in HCT116 colorectal cancer cells, we identified 21 SNHG1-reactive super-enhancers (Ψ-SEs) among 184 cancer-specific SEs, at which SNHG1 physical contacts co-occur with SNHG1-correlated histone modifications (HiMoRNA peaks), predominantly H3K4me1 (permutation p = 0.001, fold enrichment = 2.03). Comparison with 4145 lncRNAs demonstrated that epigenetic correlations alone do not distinguish SNHG1; instead, the addition of the contact layer is required to delineate the Ψ-SE set. Differential expression (DESeq2) and co-expression analyses in 471 TCGA-COAD tumor samples identified 12 Ψ-SE target genes (including CDC20, PDP1, and TOP1) consistently upregulated in both HCT116 cells and patient tumors and positively correlated with SNHG1, with the co-expression signal robust to tumor purity correction. The proposed Ψ/Ω classification provides a generalizable framework for prioritizing super-enhancers at which lncRNA–chromatin interactions may shape the local epigenetic environment across cancer types. Full article

Background/Objectives: Nuclear receptor corepressors NCOR1 and NCOR2 are key regulators of transcriptional repression, chromatin remodelling, and immunometabolic signalling. While NCOR1 has already been linked to vascular biology, its relevance in abdominal aortic aneurysm (AAA) remains unclear, particularly for NCOR2. This study aimed to investigate the expression, cellular localisation, and molecular interactions of NCOR1/2 in human AAA tissue. Methods: Human AAA samples (elective and ruptured) (n = 45) and non-aneurysmal control aortas (n = 18) were obtained from our Swiss Vascular Biobank. Transcriptomic profiling was performed using ribosomal RNA-depleted RNA sequencing. Differential expression and correlation analyses were performed using DESeq2/EdgeR and Spearman rank correlation with Benjamini–Hochberg correction. Cellular localisation was assessed through immunohistochemistry (IHC). Results: Bulk transcriptomic analyses showed no significant differences in NCOR1 or NCOR2 expression between AAA and controls. IHC revealed that NCOR1 was found in endothelial cells (ECs), smooth muscle cells (SMCs), and inflammatory infiltrates, while NCOR2 was primarily associated with macrophages. Correlation analyses suggest that NCOR1 interacts with various cellular markers, proteolytic enzymes, inflammatory mediators, and epigenetic regulators, including the lncRNA MALAT1. NCOR2 showed distinct associations with remodelling enzymes, TGFB1 signalling, selective epigenetic modifiers, and lncRNA H19. Conclusions: The lack of transcriptional differences in NCOR1 and NCOR2 between AAA and controls does not exclude cell-type-specific regulation or functional relevance. The specific cellular distributions and molecular associations in human AAA imply that NCOR1 and NCOR2 play non-redundant roles in vascular remodelling, inflammation, and epigenetic regulation. Our findings highlight NCOR pathways as potential modulators of AAA pathophysiology and promising targets for future therapies. Full article