Functional & Integrative Genomics最新文献

{"title":"LncRNA H19 promotes vascular remodeling by inhibiting MFN2","authors":"Shu-Yan Yang,&nbsp;Li Meng,&nbsp;Si-Fan Wang,&nbsp;Ying-Qing Xie,&nbsp;Li-Yun Yang,&nbsp;Sen Wang,&nbsp;Zhao-Yi Wang,&nbsp;Xu-Zhe Li,&nbsp;Yi-Ming Li,&nbsp;Ya-Xing Xu,&nbsp;Xin Xu,&nbsp;Yang Li","doi":"10.1007/s10142-026-02043-3","DOIUrl":"10.1007/s10142-026-02043-3","url":null,"abstract":"<div><p>Neointimal hyperplasia, featuring excessive proliferation and migration of vascular smooth muscle cells (VSMCs), is crucial in vascular remodeling diseases. Long non-coding RNA (lncRNA) <i>H19</i> promotes vascular remodeling, yet underlying mechanism<b>s</b> remain incompletely elucidated. Here, we investigated whether <i>H19</i> acts via its derivative miR-675-5p. Bioinformatics found a conserved <i>H19</i>/miR-675-5p/MFN2 (mitofusin 2) axis. Cell assays were performed to evaluate the effects of <i>H19</i> and miR-675-5p on VSMC proliferation and migration. The dual-luciferase reporter gene assay was used to assess the interaction between miR-675-5p and <i>Mfn2</i> mRNA. The mouse model of common carotid artery ligation was used to evaluate the role of <i>H19</i> in neointimal hyperplasia. Our data suggested that knockdown of <i>H19</i> inhibited VSMC proliferation and migration, as well as neointimal hyperplasia. Mechanistically, <i>H19</i> regulated MFN2 through miR-675-5p, leading to ERK1/2 (extracellular signal-regulated kinase 1/2) activation. In conclusion, we suggest that targeting the <i>H19</i>/miR-675-5p/MFN2/ERK1/2 axis may help to treat vascular remodeling diseases.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965987","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":"Cross-talk between GLI2 and FOXC1 promotes osteoarthritis-like cartilage catabolism and in vivo joint degeneration","authors":"Jia Fang,&nbsp;He-Bei He,&nbsp;Yi-Xin Yang,&nbsp;Shi-Long Lin,&nbsp;Yue-Lin Liu,&nbsp;Min Du,&nbsp;Xiao-Fei Zheng,&nbsp;Han-Yu Lu","doi":"10.1007/s10142-026-02056-y","DOIUrl":"10.1007/s10142-026-02056-y","url":null,"abstract":"<div><p>Osteoarthritis (OA) is a degenerative joint disease with limited disease-modifying therapies. This study investigated the roles of GLI family zinc finger 2 (GLI2) and Forkhead box C1 (FOXC1) in OA pathogenesis. Synovial fluid and cartilage were obtained from patients with knee OA who underwent total knee arthroplasty. The human chondrosarcoma cell line SW1353 was stimulated with OA synovial fluid to establish an in vitro model. Gain- and loss-of-function studies were performed using short hairpin RNA and overexpression plasmids. A rat papain-induced model was used for in vivo validation. OARSI scoring was performed by three observers on three sections per animal. GLI1, GLI2, and FOXC1 expression positively correlated with OA severity. In SW1353 cells, GLI2 and FOXC1 promoted catabolic changes and activated Wnt/β-catenin and BMP signaling. Silencing GLI2 or FOXC1 attenuated these phenotypes. Mechanistically, FOXC1 inhibited GLI2 ubiquitination by promoting JNK phosphorylation. Rescue experiments confirmed that FOXC1 exerted its effects primarily through GLI2. In vivo, sonic hedgehog inhibition or GLI2 knockdown ameliorated cartilage degeneration, as quantified by OARSI scoring. FOXC1 stabilizes GLI2 by suppressing its ubiquitination via enhanced JNK phosphorylation. The FOXC1-GLI2 axis forms a positive feedback loop that activates Wnt/β-catenin and BMP signaling, therefore representing a candidate molecular target for OA.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149132578","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":"Pan-genomics and multi-omics for deciphering genetic variation and accelerating genetic improvement in ruminant livestock","authors":"Diba Dedacha Jilo,&nbsp;Belete Kuraz Abebe,&nbsp;Waheed Ullah,&nbsp;Juntao Guo,&nbsp;Jianfang Wang,&nbsp;Haobin Ma,&nbsp;Liu Yiheng,&nbsp;Gong Cheng,&nbsp;Huanhuan Cui,&nbsp;Linsen Zan","doi":"10.1007/s10142-026-02042-4","DOIUrl":"10.1007/s10142-026-02042-4","url":null,"abstract":"<div><p>Livestock reference genomes have transformed the discovery of variants associated with production, reproduction, health, and environmental adaptation. Nevertheless, a single linear reference represents only one mosaic haplotype and incompletely captures sequence diversity within a species, particularly structural variants, copy-number changes, repeat-rich regions, and breed-specific sequences. Pangenomes address this limitation by integrating multiple high-quality assemblies or population-scale variants into a unified sequence or graph representation. Concurrently, multi-omics approaches connect genomic variation with transcriptomic, epigenomic, manuscriptproteomic, metabolomic, and microbiome responses, thereby improving biological interpretation of genotype–phenotype relationships. This review synthesizes recent progress in livestock pangenomics and multi-omics, with emphasis on cattle, goats, sheep, water buffalo, and chickens. It describes advances in long-read and haplotype-resolved sequencing, graph construction, structural-variant discovery and genotyping, functional annotation, and integrative analysis. Recent pangenome studies have uncovered substantial non-reference sequence, reduced reference bias, identified breed- and population-specific structural variants, and resolved candidate variants underlying pigmentation, body size, tail morphology, cashmere production, altitude adaptation, and other economically relevant traits. However, translation into routine breeding remains constrained by uneven population representation, inconsistent structural-variant definitions, limited functional annotation, computational demands, and insufficient validation across environments. Future progress will depend on diverse near-complete assemblies, graph-aware imputation and genomic prediction, long-read transcriptomics, single-cell and spatial omics, rigorous causal validation, and open, interoperable resources. Together, these developments can support more accurate, resilient, and biologically informed livestock improvement. Importantly, current dairy-cattle evidence indicates that pangenome-derived structural variants can substantially improve variant discovery and functional interpretation while yielding only marginal average gains in routine genomic prediction, favoring targeted augmentation rather than wholesale replacement of established SNP-based evaluations.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927270","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":"Mechanism of Shoutai Wan against recurrent spontaneous abortion: regulation of decidual vascular remodeling via ERβ-ANGPT2 signaling axis","authors":"Xiaoli Lv,&nbsp;Yuexi Zhou,&nbsp;Ruili Li,&nbsp;Qiang Wang,&nbsp;Zhanli Wang,&nbsp;Xiao Li,&nbsp;Xia Ji,&nbsp;Songping Luo,&nbsp;Jinying Fu","doi":"10.1007/s10142-026-02022-8","DOIUrl":"10.1007/s10142-026-02022-8","url":null,"abstract":"<div><p>Shoutai Wan (STW), a classic traditional Chinese medicine formula used to tonify the kidney and prevent miscarriage, has been widely applied in the clinical management of recurrent spontaneous abortion (RSA). Increasing clinical evidence supports its efficacy in reducing miscarriage rates and improving pregnancy outcomes. However, the molecular basis by which STW alleviates defective decidual vascular remodeling in unexplained RSA remains insufficiently understood. Clinically, decidual ERβ and ANGPT2 expression, as well as serum estradiol, ANGPT2 and VEGFA levels were significantly decreased in RSA patients, accompanied by reduced decidual microvascular density. Furthermore, ERβ expression was positively correlated with ANGPT2 and microvascular density. In vivo, STW dose-dependently reduced embryo loss in RSA mice, repaired the damaged decidual-placental interface structure, and improved vascular maturation, structural stability and endothelial-pericyte ultrastructural connections. Mechanistically, STW upregulated ERβ expression. We demonstrated that ERβ binds to the ANGPT2 promoter, suggesting transcriptional upregulation of ANGPT2, thereby activating Tie2 and the downstream PI3K/AKT pathway and increasing NO and VEGFA secretion. In vitro, hypoxia inhibited ERβ nuclear translocation and ANGPT2 secretion in mDSCs, while STW-containing serum reversed these abnormalities. ERβ knockdown impaired the pro-angiogenic capacity of mDSCs, which was partially rescued by exogenous ANGPT2 supplementation. Network pharmacology predicted that STW targets were mainly enriched in PI3K-Akt, estrogen, VEGF and angiogenesis-related pathways. Transcriptomic GSEA further revealed that the gene signatures of angiogenesis and PI3K-Akt signaling were markedly suppressed in the RSA model, and STW treatment significantly normalized these transcriptional signatures.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927781","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":"METTL14 alleviates pyroptosis of placental trophoblasts in gestational diabetes mellitus through the lncRNA MEG8/WNT7A axis via m6A modification","authors":"Xue-Li Gao,&nbsp;Yun-Tao Wei,&nbsp;Xiao-Yan Yu","doi":"10.1007/s10142-026-01986-x","DOIUrl":"10.1007/s10142-026-01986-x","url":null,"abstract":"<div><p>Gestational diabetes mellitus (GDM) is a pregnancy complication associated with abnormal placental trophoblast function. Pyroptosis has been implicated in GDM pathogenesis, yet the role of m6A modification in this process remains unclear. We hypothesized that METTL14 regulates trophoblast pyroptosis through m6A-dependent modulation of the lncRNA MEG8/WNT7A axis. This study investigated the mechanism of METTL14 in pyroptosis of placental trophoblasts in GDM. HG-treated HTR8/SVneo cells were used as a cell model. METTL14, WNT7A, and lncRNA MEG8 expression was detected by RT-qPCR and western blot. Placental damage, cell injury, and pyroptosis markers were assessed. YTHDF2-mediated m6A enrichment on lncRNA MEG8, the interaction between lncRNA MEG8 and EZH2, and H3K27me3 enrichment on the WNT7A promoter were analyzed. Results showed that lncRNA MEG8 was upregulated, while METTL14 and WNT7A were downregulated. METTL14 overexpression reduced placental damage and trophoblast pyroptosis. Mechanistically, METTL14 suppressed lncRNA MEG8 expression through YTHDF2-mediated m6A methylation. Reduced lncRNA MEG8 decreased EZH2 recruitment to the WNT7A promoter, lowered H3K27me3 levels, and consequently promoted WNT7A expression. Rescue experiments confirmed that lncRNA MEG8 overexpression or WNT7A knockdown attenuated the suppressive effect of METTL14 on pyroptosis. In conclusion, METTL14 acts as an upstream regulator that inhibits trophoblast pyroptosis and ameliorates GDM-induced damage through the lncRNA MEG8/WNT7A axis via YTHDF2-mediated m6A modification, highlighting METTL14 as a potential therapeutic target.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927780","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":"Integrated molecular and immune profiling identifies FOXA1 as a complementary co-target to MUC1 for bispecific immunotherapy in breast cancer","authors":"Debolina Chakraborty,&nbsp;Subhadip Kundu,&nbsp;Vinit Gupta,&nbsp;Mansi Patel,&nbsp;Sudhir Kumar Rawal,&nbsp;Samson Mani","doi":"10.1007/s10142-026-02030-8","DOIUrl":"10.1007/s10142-026-02030-8","url":null,"abstract":"<div><p>In breast cancer immunotherapy, Mucin 1 (MUC1) is a well-established target with promising preclinical results; however, single targeting of MUC1 has demonstrated limited efficacy in clinical trials, largely due to tumor heterogeneity, diverse glycosylation patterns, and an immunosuppressive TME. Identification of complementary co-targets enables bi-specific or dual-target immunotherapy, limiting antigen escape, improving specificity, and reducing relapse. Here, we employed a comprehensive multi-layered analytical approach to evaluate MUC1 expression, clinical relevance, and methylation status, followed by systematic screening of MUC1-correlated genes. Antigenicity prediction and protein–protein interaction analyses identified Forkhead Box A1 (FOXA1) as a potential functional partner. Expression analysis revealed concordant patterns of MUC1 and FOXA1 across breast cancer samples, while network mapping demonstrated shared interactions with adhesion-associated proteins, including CTNNB1, CTNND1, and CDH1, suggesting roles in epithelial organization and tumor progression. Further validation using gene expression datasets from Indian breast cancer cohorts confirmed consistent expression and correlation patterns, supporting reproducibility across populations. Immune profiling revealed an inverse association between MUC1-FOXA1 co-expression and immune-related gene signatures, with high co-expression linked to reduced infiltration of dendritic cells, CD4⁺ and CD8⁺ T cells, macrophages, and natural killer cells, indicative of an immunosuppressive microenvironment. Negative correlations with MHC Class I genes further suggested impaired antigen presentation. Epitope prediction identified high-affinity peptides from both targets with strong MHC Class I binding potential. Collectively, these findings support the associated role of MUC1 and FOXA1 as dual immunotherapeutic targets in breast cancer.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927862","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":"Integrated single-cell and spatial transcriptomic analyses reveal malignant epithelial glycolytic heterogeneity and spatial niche remodeling during colorectal cancer progression","authors":"Jinyun Xiao,&nbsp;Shanshan Heng,&nbsp;Jiayu Li,&nbsp;Shaozhuo Xie,&nbsp;Liangzhi Li,&nbsp;Jiajia Chen,&nbsp;Jie Wu,&nbsp;Yuxin Lin,&nbsp;Xin Qi","doi":"10.1007/s10142-026-02039-z","DOIUrl":"10.1007/s10142-026-02039-z","url":null,"abstract":"<div><p>Colorectal cancer (CRC) progression is shaped by metabolic reprogramming and complex interactions within the tumor microenvironment. However, the cellular heterogeneity, spatial organization, and clinical relevance of glycolytic activity in CRC remain incompletely understood. In this study, we integrated single-cell RNA sequencing, bulk transcriptomics, and spatial transcriptomics data to systematically characterize glycolytic heterogeneity in CRC. Glycolytic activity was quantified using five independent scoring methods, consistently showing that epithelial cells exhibited the highest glycolytic activity across the two single-cell cohorts. Stratification of CopyKAT-verified aneuploid malignant epithelial cells into high-glycolysis (HG) and low-glycolysis (LG) subgroups by glycolysis scores revealed that HG cells exhibited higher stemness scores and chromosomal copy number variations. Cell-cell communication analysis revealed that, compared with LG cells, HG cells exhibited increased interaction frequency and strength with immune and stromal populations, indicating enhanced malignant epithelial-microenvironment crosstalk. Spatial transcriptomics analyses further revealed that glycolytic activity varied across normal colorectal tissue, primary CRC, and colorectal liver metastases, accompanied by progressive remodeling of epithelial-associated spatial niches and MIF-mediated intercellular communication. Bulk transcriptomic analysis identified a glycolysis-related prognostic signature with robust predictive performance, which served as an independent prognostic factor for overall survival in CRC cohorts. Collectively, these findings indicate that glycolytic heterogeneity is a key feature of CRC malignant epithelial cells and is closely associated with tumor progression, microenvironmental remodeling, and clinical outcomes.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917937","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":"Integrated transcriptomic and metabolomic analysis reveals candidate regulatory networks associated with starch accumulation in tetraploid potato","authors":"Huanhuan Lian,&nbsp;Chao Zhang,&nbsp;Yongzhen Ma,&nbsp;Guangji Ye,&nbsp;Shenglong Yang,&nbsp;Yun Zhou,&nbsp;Wang Su,&nbsp;Jian Wang","doi":"10.1007/s10142-026-02036-2","DOIUrl":"10.1007/s10142-026-02036-2","url":null,"abstract":"<div><p>Potato (<i>Solanum tuberosum</i> L.) tuber starch is a major determinant of crop quality and industrial value, yet the regulatory mechanisms underlying starch accumulation in autotetraploid cultivars remain poorly resolved. Here, we performed integrated transcriptomic and metabolomic analyses using a segregating tetraploid population derived from parents with contrasting starch content. Extreme phenotypes were selected to systematically dissect the molecular basis of starch accumulation. Transcriptome profiling revealed extensive transcriptional reprogramming between high- and low-starch genotypes, with differentially expressed genes significantly enriched in carbohydrate metabolism, particularly the starch and sucrose metabolism pathway. Notably, multiple transcription factor families, including AP2/ERF, MYB, and bHLH, were prominently represented, suggesting coordinated regulatory control. Metabolomic analysis identified substantial metabolic divergence, with differentially accumulated metabolites predominantly enriched in starch and sucrose metabolism as well as secondary metabolic pathways. Most metabolites exhibited negative associations with starch content, indicating competitive carbon allocation between primary and secondary metabolism. Integrative multi-omics analysis further resolved a core regulatory module comprising key structural genes and transcription factors tightly associated with starch-related metabolites. In particular, genes involved in sucrose cleavage and ADP-glucose metabolism, together with trehalose-6-phosphate synthase (TPS) and UDP-glucose-associated pathways, emerged as critical nodes linking carbon flux to starch biosynthesis. Correlation network analysis suggested that AP2/ERF-, MYB-, and bHLH-type transcription factors modulate these pathways by coordinating structural gene expression and metabolic flux distribution. Collectively, our study establishes a transcriptional–metabolic framework for starch accumulation in tetraploid potato, highlighting the central role of carbon allocation and signaling intermediates in shaping starch content, and providing candidate targets for molecular breeding and genome editing.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910496","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":"Integrative pooled transcriptomic analysis reveals shared and distinct molecular signatures in adult T-cell leukemia/lymphoma and peripheral T-cell lymphoma","authors":"Mohammad Mehdi Akbarin,&nbsp;Zahra Farjami,&nbsp;Hugo Ramírez Álvarez","doi":"10.1007/s10142-026-02041-5","DOIUrl":"10.1007/s10142-026-02041-5","url":null,"abstract":"<div><p>Adult T-cell leukemia/lymphoma (ATLL) and peripheral T-cell lymphomas (PTCLs) are aggressive neoplasms of mature T cells with poor prognosis and limited therapies. ATLL originates from HTLV-1 infection, while PTCL comprises heterogeneous subtypes without a defined etiologic factor. Comparative molecular profiling of these malignancies remains limited. We conducted an integrative pooled transcriptomic analysis of publicly available Gene Expression Omnibus (GEO) microarray datasets to compare ATLL, PTCL, and normal T-cell samples. Differential expression, functional enrichment, and protein–protein interaction (PPI) network analyses were performed using STRING, Cytoscape, and Gephi. Key hub genes and functional modules were further analyzed through KEGG and Enrichr databases. Comparative analyses revealed upregulation of extracellular matrix (ECM) components (<i>COL1A1</i>,<i> COL3A1</i>,<i> FN1</i>,<i> SPARC</i>,<i> THBS1</i>) and immune-regulatory molecules (<i>CD163</i>,<i> CXCL12–CXCR4</i>, complement subunits). Shared pathways included ECM–receptor interaction, focal adhesion, and PI3K–Akt signaling. PTCL showed enrichment in coagulation and angiogenesis, while ATLL displayed distinct enrichment of cytoskeletal, chemokine, immune-regulatory, and signaling-associated pathways. PPI networks identified ECM and chemokine signaling as key hubs, with subtype-specific modules related to immune regulation, proliferation, and metabolism. This integrative approach uncovers common and distinct oncogenic programs in ATLL and PTCL, emphasizing ECM remodeling and immune modulation as shared hallmarks. Hub genes such as <i>COL1A1</i>,<i> FN1</i>, and <i>CXCL12–CXCR4</i> may represent candidate molecular signatures that warrant validation in independent patient cohorts and functional studies before their clinical utility can be established.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-026-02041-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917930","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":"Exploring the transcriptional crosstalk between adipose tissue and locoregional recurrence in breast cancer using independent component analysis","authors":"Marlous Arjaans,&nbsp;Bert van der Vegt,&nbsp;Renske Linstra,&nbsp;Rudolf S. N. Fehrmann,&nbsp;Arkajyoti Bhattacharya","doi":"10.1007/s10142-026-02012-w","DOIUrl":"10.1007/s10142-026-02012-w","url":null,"abstract":"<div><p>Locoregional recurrence (LRR) poses a persistent clinical challenge in breast cancer, with emerging evidence implicating the tumor-associated adipose tissue in modulating recurrence risk. This study investigates shared transcriptional programs between adipose tissue and breast tumors and examines their association with disease-free survival (DFS), particularly in the context of reconstructive surgery where adipose tissue from different body compartments are commonly used. We analyzed bulk gene expression data from 5,691 breast tumors and 978 human adipose tissue samples from different body compartments using consensus-independent component analysis (c-ICA) to identify transcriptional components (TCs). Gene set enrichment analysis (GSEA) and copy number alteration profiling were used for biological annotation. Associations between TCs and DFS were evaluated through univariate Cox regression. Key findings were validated using spatial transcriptomic and single-cell RNA sequencing datasets. Among the 411 TCs identified, 332 showed biological enrichment, and 35 were significantly associated with DFS. Four DFS-associated TCs (TC257, TC350, TC371, TC400) were enriched for adipogenesis-related genes and exhibited heightened activity in high-grade, triple-negative tumors and in patients with elevated BMI. Notably, TC350 was highly active in adipose tissue from common reconstructive donor sites (abdomen, omentum, subcutis) but not in native breast adipose tissue. Spatial transcriptomic and single-cell analyses confirmed the increased activity of these adipogenesis-related TCs in tumor regions and adipose cells. TC350 included <i>FABP4</i>, a gene previously linked to poor prognosis in breast cancer and considered as a potential new therapeutic target. Adipose tissue-derived transcriptional programs influence breast cancer prognosis and this seems to differ by tissue origin. These findings generate a hypothesis that donor site selection for adipose tissue in reconstructive surgery may impact LRR risk through adipogenesis-associated mechanisms. Further research is warranted to elucidate the biological and clinical implications of adipose–tumor transcriptional interactions.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-026-02012-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910498","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}