Mammalian Genome最新文献

{"title":"Screening for candidate genes and cell populations associated with atherosclerotic calcification using single-cell RNA sequencing.","authors":"Huai Wu Yuan, Weiye Wang, Wei Cheng, Hongzhe Wang, Boyan Song, Tian Xiang Chen, Guo Ping Peng","doi":"10.1007/s00335-026-10262-z","DOIUrl":"https://doi.org/10.1007/s00335-026-10262-z","url":null,"abstract":"<p><p>Calcification often occurs as a characteristic pathological manifestation in the progression of atherosclerosis (AS) plaques, but its mechanism is not fully understood yet. The purpose of this research was to supplement the exploration of key candidate genes and key cells involved in the calcification process of AS, building on existing insights into its underlying mechanisms. Through the examination of our internally generated single‑cell RNA sequencing (scRNA-seq) dataset derived from human carotid plaque samples, pivotal cellular populations associated with AS calcification were successfully identified. Following this identification, a comprehensive analytical approach was employed, incorporating differential gene expression profiling alongside the establishment of protein-protein interaction (PPI) networks, thereby enabling the extraction of critical genetic markers within these cellular subsets. Furthermore, a molecular regulatory framework was assembled, aiming to elucidate the mechanistic pathways through which these genetic determinants contribute to the calcification phenomena in AS pathology. Moreover, analysis of cell communication was applied to explore the interactions among cells. Pseudo-time analysis was employed to explore the expression of key candidate genes during the differentiation of key cells. Finally, monocytes were identified as key cells. WARS1, IFITM1, ANXA1, ADGRE2, and S100P were identified as key candidate genes. Moreover, 115 transcription factors such as THRB and 118 miRNAs such as hsa-miR-196a-5p were predicted to be associated with the key candidate genes. Across both calcified and non-calcified control specimens, the cellular communication between endothelial cells and natural killer (NK) T cell populations was consistently orchestrated via the PPBP-CXCR2 signaling axis. During monocytic differentiation trajectories, ADGRE2 expression exhibited a biphasic pattern characterized by initial gradual elevation followed by subsequent decline. Conversely, both ANXA1 and S100P demonstrated progressive upregulation throughout the differentiation process. The expression of IFITM1 and WARS1 first decreased, then increased, and finally decreased again. The present investigation successfully pinpointed five critical genes alongside one key cellular population, collectively providing potential molecular insights and candidate targets for further investigation into AS calcification.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide meta-analysis with 1,590,596 individuals identifies 12 novel risk loci for systemic lupus erythematosus.","authors":"Gaizhi Zhu, Wenting Su, Jiahui Deng, Bing Zhai, Ran Gao, Jinming Qiu, Keqi Gu, Ziqing Bian, He Xiao, Guoming Luan, Renxi Wang","doi":"10.1007/s00335-026-10266-9","DOIUrl":"10.1007/s00335-026-10266-9","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a chronic life-threatening and relapsing-remitting multisystem autoimmune disease. However, the genetic susceptibility of SLE has not been fully elucidated. This study will explore the genetic risk loci of SLE. We performed the larger multi-ancestry meta-analysis of genome-wide association study (GWAS) including 22,494 cases with SLE and 1,568,102 healthy controls. Multi-ancestry meta-analysis identified 101 risk loci including 12 novel loci. Across 101 loci, 2,209 likely causal genes are indicated and 265 genes are prioritized, based on eight biological prioritization criteria. The most significantly locus were located on 6p21.32, whereas the highest-ranked candidate causal gene was BLK. Heritability analyses demonstrated a liability scale of the heritability is 25.49%, whereas an estimated 1.25 million effective sample sizes would be necessary to explain 90% of phenotypic variance. Gene enrichment, gene-set analyses, and the genetic correlation revealed that SLE-related genes were enriched in whole blood and spleen, promoted MHCII-related pathways, JAK-STAT signaling, abnormal activation of T and B cells, autoantibodies such as anti-nuclear antibody and anti-neutrophil antibody production, and had a positive genetic correlation with autoimmune diseases (e.g., rheumatoid arthritis), mental and neurological disorders (e.g., schizophrenia), and cardiovascular diseases (e.g., hypertension). Finally, druggable, gene-drug interaction, drug target, and drug repurposing analysis suggested some potential targets (e.g., BLK) and drug (e.g., riboflavin) repurposing for SLE. In conclusion, we identified 101 risk loci including 12 novel loci for SLE. Based on 101 loci, we provided new biological insights, some potential targets, and drug repurposing for SLE.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The future objectives of the International Mouse Phenotyping Consortium (IMPC): functional evaluation of human disease-relevant cis-regulatory elements in the mouse genome.","authors":"Naoki Kubo, Akiko Oguchi, Hiroshi Masuya, Takanori Amano, Akihiko Sakashita, Hideya Kawaji, Takeya Kasukawa, Shinya Oki, Shinya Ayabe, Toyoyuki Takada, Atsuo Ogura, Kimiko Inoue, Yasuhiro Murakawa, Masaru Tamura, Atsushi Yoshiki, Toshihiko Shiroishi","doi":"10.1007/s00335-026-10258-9","DOIUrl":"10.1007/s00335-026-10258-9","url":null,"abstract":"<p><p>The International Mouse Phenotyping Consortium (IMPC) has established a large-scale functional genomics resource by systematically generating and phenotyping knockout mouse lines, linking gene function to mammalian phenotypes. However, interpreting disease-associated non-coding variants remains particularly challenging due to their abundance, context-dependent activity, and the complexity of gene regulation. Genome-wide association studies (GWAS) have shown that many disease-associated loci map to non-coding regions. In addition, recent large-scale consortia have catalogued millions of candidate cis-regulatory elements (CREs) across mammalian genomes; however, predicting which elements contribute to disease-relevant gene regulation and organismal phenotypes remains difficult. Together, these observations highlight disease-relevant CREs as an important but still underexplored component of human disease mechanisms. In this white paper, we outline strategies to address this challenge: (i) prioritization of disease-relevant candidate CREs, (ii) genome editing in mice to functionally evaluate CREs, and (iii) the establishment of interdisciplinary working groups. By extending its activities beyond protein-coding sequences, the IMPC has a unique opportunity to define the functional and phenotypic impact of disease-relevant CREs in vivo at scale, thereby improving our understanding of how non-coding regulatory elements contribute to mammalian phenotypes and human disease.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13400468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Draft nuclear and complete mitochondrial genome assemblies of the flare-horned markhor (Capra falconeri): genomic resources for conservation and phylogenetics.","authors":"Javeria Wali, Muhammad Waqas, Azhar Hussain Shah, Inam Ullah, Asif Mir, Zunnan Huang, Amjad Ali","doi":"10.1007/s00335-026-10261-0","DOIUrl":"https://doi.org/10.1007/s00335-026-10261-0","url":null,"abstract":"<p><p>The flare-horned markhor (Capra falconeri), a near-threatened mountain ungulate endemic to the Western Himalayas, remains vulnerable to habitat fragmentation, human disturbance, and environmental change. Although localized conservation efforts have stabilized some populations, genomic resources for this species remain limited. Here, we report nuclear and mitochondrial genome assemblies for C. falconeri, including a nuclear genome assembly (GCA_038502695.1) and a complete mitochondrial genome (OR799853.1), and place these data within an ecological context derived from field surveys. A structured winter survey conducted between 2020 and 2022 documented 225 individuals across 14 sites, indicating a demographically stable population with marked spatial heterogeneity. Genome-completeness assessment with BUSCO indicated that the short-read nuclear assembly is a fragmented draft (49.4% complete), and should be regarded as a preliminary genomic resource rather than a reference-quality genome. The complete mitochondrial genome is 16,639 bp in length and exhibits conserved gene organization and pronounced AT bias; comparison with the reference mitogenome identified high-confidence coding-region substitutions, exclusively transitions, distributed across the major mitochondrial protein-coding gene groups. Codon usage analyses revealed moderate bias, whereas Ka/Ks ratios across the mitochondrial protein-coding genes were consistently below one, indicating pervasive purifying selection. Comparative phylogenetic analyses based on mitochondrial and nuclear data resolved the evolutionary placement of C. falconeri within the genus Capra. Together, these results provide genomic assemblies supported by ecological context and establish a foundation for future comparative, population, and conservation genomics studies of this species.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics analysis of HLTF context-dependent regulation across TCGA cohorts revealed its potential as new biomarker in tumour.","authors":"Alessia Canevotti, Marija Tursunović, Wendalina Tigani, Graziano Pesole, Matteo Chiara, Matteo De March","doi":"10.1007/s00335-026-10257-w","DOIUrl":"10.1007/s00335-026-10257-w","url":null,"abstract":"<p><p>The SNF2-family Helicase-Like Transcription Factor (HLTF) has been implicated in tumorigenesis, with evidence suggesting both tumour-suppressive and oncogenic functions. To clarify the nature of this increasingly emerging double function, we analysed the full HLTF's alterome across TCGA cohorts combining first gene expression with genomic and epigenomic layers of de-regulation, and investigating further their determinants through the integration of DNA methylation profiles - both at promoter-proximal and distal regions, the copy-number alterations, and all somatic mutations. This multi-layered analysis highlighted specific context-dependent HLTF's regulatory configurations across human cancers, even modulated by either dosage effects or loss-of-function events. The clinical relevance of HLTF's alterations, identified through tumour-specific associations with patient outcomes, supports its potential as new biomarker in cancer overall.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13400721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia-induced mechanism of TNBC promoting tumour cell proliferation through exosomal miRNA.","authors":"Xiangxin Zheng, Peng Yang, Sai Zhou, Xiaochao Zhu, Xiaoqing Guan, Guoqin Jiang","doi":"10.1007/s00335-026-10260-1","DOIUrl":"https://doi.org/10.1007/s00335-026-10260-1","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC), characterized by the absence of ER, PR, and HER2 expression, is associated with aggressive clinical behavior and limited treatment options. Hypoxia in the tumor microenvironment (TME) may influence intercellular communication through exosomes. In this study, we investigated whether hypoxia-derived exosomes regulate malignant phenotypes of TNBC cells through exosomal miRNAs. Exosomes derived from hypoxic TNBC cells increased proliferation, migration, and invasion of recipient TNBC cells compared with normoxia-derived exosomes. Small RNA sequencing and RT-qPCR validation showed enrichment of miR-4791 in hypoxia-derived exosomes. Functional assays indicated that miR-4791 overexpression promoted TNBC cell proliferation, whereas miR-4791 inhibition reduced proliferative capacity. Mechanistically, miR-4791 directly targeted the 3'UTR of CTCFL and was associated with reduced PTEN expression. Rescue experiments suggested that restoration of CTCFL or PTEN partially attenuated miR-4791-associated malignant phenotypes in vitro and in vivo. Analysis of GSE19536 showed higher miR-4791 expression in breast cancer tissues than in normal tissues; however, the number of normal samples was limited. Survival analysis using GSE19783 indicated that higher miR-4791 expression was associated with poorer survival, although the prognostic ROC performance was weak-to-modest. Overall, these findings suggest that hypoxia-derived exosomal miR-4791 may contribute to TNBC progression, at least in part, through a CTCFL/PTEN-related mechanism.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semi-supervised ensemble learning with interval type-2 fuzzy-rough sets for Parkinson's disease prediction from multi-omics.","authors":"Ambika Hazarika, Ansuman Kumar, Anindya Halder","doi":"10.1007/s00335-026-10256-x","DOIUrl":"https://doi.org/10.1007/s00335-026-10256-x","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a disorder involving progressive degeneration of the nervous system. Its clinical signs typically become noticeable only after substantial impairment has occurred in the substantia nigra, a brain region involved in motor control. Therefore, early and accurate prediction of PD based on molecular alterations is essential for proper diagnosis and improved patient outcomes. In this context, feature-level multi-omics integration has become a useful strategy because it combines molecular information from multiple biological levels and may support a broader understanding of disease progression. This study proposes a novel technique called Semi-supervised Ensemble Learning with Interval Type-2 Fuzzy-Rough Sets (SSEnIT2FRS) for PD prediction from multi-omics data, which leverages interval type-2 fuzzy-rough sets to achieve early and accurate prediction. The type-2 fuzzy-rough set enhances the handling of uncertainty and vagueness present in real-world biological datasets, while the ensemble approach improves predictive robustness by combining the decisions of multiple base classifiers. Furthermore, the inclusion of semi-supervised learning addresses the scarcity of labeled samples. The experimental findings indicate that the proposed method outperforms nine existing methods across all evaluation metrics, achieving the highest accuracy of 98.49%, with precision 0.9820, recall 0.9865, macro [Formula: see text]-score 0.9836, micro [Formula: see text]-score 0.9842, kappa 0.9672, specificity 0.9953, and AUC of 0.9969 on the multi-omics dataset. Boxplots, paired t-test results, confidence interval analysis, and SHAP-based explanations further justify the superior performance, robustness, statistical significance, and interpretability of the proposed method. Therefore, the proposed method could be an effective computational technique for identifying PD at an early stage from multi-omics data.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent homology of blood gene co-expression networks reveals reduced cycle structure in autism spectrum disorder: a multi-cohort analysis.","authors":"Mehmet Ali Balcı, Ömer Akgüller","doi":"10.1007/s00335-026-10259-8","DOIUrl":"https://doi.org/10.1007/s00335-026-10259-8","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) exhibits substantial molecular heterogeneity that challenges traditional gene-centric analyses. We applied persistent homology of the graph 1-skeleton to characterize co-expression cycle structure in mutual information-based gene networks in ASD. Using transcriptomic data from brain tissue and peripheral blood, we constructed MI networks from the 500 most variable genes, computed Betti-1 numbers across 30 filtration steps, and assessed significance via 10,000-permutation testing. We note that this approach computes first homology on the 1-skeleton, not the full flag/clique complex; this distinction is made explicit throughout. ASD peripheral blood networks exhibited nominally significant topological reorganization relative to neurotypical controls, with a 20.4% reduction in the area under the Betti-1 curve. After excluding 44 redundant SNORD115-family probes to address microarray probe-redundancy concerns, the finding strengthened substantially to [Formula: see text], which we consider the primary result. This indicates that regulatory cycle structure accumulates less readily in ASD blood co-expression networks across the full filtration range. Brain cortex networks showed no significant topological differences; however, a post-hoc power analysis indicates the brain cohort has only ∼ 36% power to detect the blood-magnitude effect, so this null result should not be interpreted as evidence of preserved brain topology or tissue specificity. After SNORD115 probe exclusion, ASD hub genes form a ribosomal protein gene cluster consistent with translational dysregulation in ASD. To validate the blood finding, we applied the identical TDA pipeline to two independent blood transcriptome datasets: GSE42133 and GSE25507. Both independent cohorts exhibited the same ASD < control direction. Stouffer meta-analysis combining the z-scores from all three blood datasets, demonstrating robust directional replication of the reduced-cycle-structure signal across independent cohorts (spanning two Affymetrix platforms, Human Gene 1.0 ST and U133 Plus 2.0). These findings demonstrate that graph-filtration cycle-rank analysis detects reduced co-expression cycle structure in ASD peripheral blood, independently replicated across three blood transcriptome cohorts. The Stouffer meta-analysis substantially exceeds conventional significance thresholds and supports the potential utility of topological biomarkers in neurodevelopmental disorders.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering genetic diversity and selection footprints in Rathi cattle through ddRAD-based genome-wide analysis.","authors":"Nishu Bharia, Anal Bose, Sonali Sonejita Nayak, Divya Rajawat, Vijay Kumar, Triveni Dutt, Manjit Panigrahi","doi":"10.1007/s00335-026-10254-z","DOIUrl":"https://doi.org/10.1007/s00335-026-10254-z","url":null,"abstract":"<p><p>Rathi cattle, an indigenous Bos indicus breed of north-western India, represent a valuable genetic resource due to their adaptation to arid environments, heat tolerance and dairy potential. However, genomic information on this breed remains limited. This study provides the first double-digest restriction-site associated DNA sequencing (ddRAD) based genome-wide assessment of Rathi cattle using a large sample size. A total of 96 animals were genotyped, generating 78,193 high-quality SNPs with 96.52% alignment to the Bos taurus (ARS-UCD2.0) reference genome, guaranteeing dependable variant identification. The population exhibited moderate genetic diversity with nucleotide diversity (π = 0.33 ± 0.09) and heterozygosity (Ho = 0.291 ± 0.084; He = 0.329 ± 0.104). Runs of homozygosity (ROH) made up 5.43% of the genome, and most of them were short segments (< 2 Mb), which shows that there hasn't been much inbreeding lately (F_ROH = 0.0512). Effective population size (Ne) declined from 1454 (150 generations ago) to 94 at present, highlighting the impact of demographic bottlenecks and genetic drift. The declining Ne suggests a risk of future genetic erosion, highlighting the need for effective conservation and breeding strategies. Population structure analyses (PCA, ADMIXTURE and STRUCTURE) revealed clear genetic distinctness of Rathi from other indigenous dairy breeds, despite its composite origin. Selection signature analyses (Tajima's D, CLR, ROH islands and iHS) identified candidate regions harboring genes associated with immunity (IL2RB, USP18), reproduction (INHBA, MEI4, HBA), lactation (LRRC8D, TRERF1, CCND3) and stress adaptation (CARHSP1, ITGAV). These findings are highlighting the valuable insights about diversity, demographic history and adaptive potential of rathi and offering genomic resources for conservation, sustainable utilization and genetic improvement programs.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148411865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of shared hub genes CTNNB1, TJP1, PTK2, and TP53 associated with endothelial proliferation in infantile hemangioma and glioblastoma.","authors":"Yanli Niu, Jing Li, Liang Wang, Duoduo Li","doi":"10.1007/s00335-026-10252-1","DOIUrl":"https://doi.org/10.1007/s00335-026-10252-1","url":null,"abstract":"<p><p>Infantile hemangioma (IH) and glioblastoma multiforme (GBM) are clinically distinct but share vascular and proliferative characteristics. This study aimed to identify common transcriptional and regulatory mechanisms between IH and GBM to uncover potential hub genes driving disease progression. Transcriptomic datasets GSE127487 (IH) and GSE108476 (GBM) were analyzed using the limma package in R. Differentially expressed genes (DEGs) were overlapped to identify shared signatures. Protein-protein interaction networks were built using STRING and analyzed in Cytoscape to determine hub genes via CytoHubba. Gene expression, promoter methylation, mutation, and CNV data were validated using OncoDB, GEO2R, UALCAN, and cBioPortal. Functional enrichment and drug sensitivity analyses were performed using DAVID and GSCA. Experimental validation included siRNA knockdown or overexpression of target genes in HemSCs, HemECs, U87-MG, and LN229 cells, followed by RT-qPCR, western blot, proliferation, colony formation, and wound-healing assays. A total of 142 common DEGs were identified, with four hub genes, including TP53, CTNNB1, TJP1, and PTK2 showing consistent dysregulation. TP53 and CTNNB1 were upregulated, while TJP1 and PTK2 were downregulated in both IH and GBM. Methylation, mutation, and CNV analyses supported their regulatory involvement. Functional assays confirmed that CTNNB1 knockdown and TJP1/PTK2 overexpression suppressed proliferation and migration. This integrative study identifies CTNNB1, TJP1, PTK2, and TP53 as shared hub genes, highlighting common molecular regulators of endothelial proliferation and tumor-associated phenotypes in IH and GBM, and suggesting potential therapeutic targets.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}