{"title":"Immune-based molecular subtyping of triple-negative breast cancer via SNF-CC and functional validation of key immune-associated genes.","authors":"Pengwei Guo, Fengfei Yan, Hui Chang, Fuchun Li, Jinpeng Hu, Meizhe Liu, Aidong Li","doi":"10.1007/s10142-025-01654-6","DOIUrl":"https://doi.org/10.1007/s10142-025-01654-6","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) presents significant therapeutic challenges due to its aggressive nature and lack of targeted treatment options. Emerging evidence highlights the critical role of immune infiltration patterns in TNBC progression and prognosis, yet a comprehensive classification system integrating immune and transcriptomic features remains elusive. In this study, we employed the xCell algorithm to characterize immune infiltration across TNBC samples and utilized the Similarity Network Fusion and Consensus Clustering (SNF-CC) method to identify molecular subtypes. Our analysis revealed three distinct TNBC subtypes with marked heterogeneity in transcriptomic profiles and immune microenvironment composition. Subtype 1 exhibited high immune infiltration, while Subtype 3 demonstrated immunosuppressive characteristics. Functional enrichment analysis linked subtype-specific differentially expressed genes (DEGs) to pathways such as T-cell activation and cytokine signaling. Protein-protein interaction networks identified key hub genes (PTPRC, CD4, and UBE2C) showing elevated expression in TNBC tissues. Experimental validation in breast cancer cell lines confirmed that knockout of PTPRC, CD4, or UBE2C significantly impaired proliferation, migration, and invasion, while rescue experiments restored these oncogenic phenotypes. These findings establish an immune-based molecular subtyping framework for TNBC and uncover pivotal genes driving tumor progression. Our work provides novel insights into TNBC heterogeneity and identifies potential therapeutic targets for precision immunotherapy, advancing strategies to improve clinical outcomes in this recalcitrant malignancy.</p>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":"148"},"PeriodicalIF":3.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582776","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":"Discovering novel type I collagen fragments from Cyprinus carpio supporting bone regeneration.","authors":"Jianhua Zeng, Miao Chen, Xinglong Wang, Huan Yu, Liang Zhang, Yongxing Peng, Ping Wan, Zhongshi Huang, Fuqiang Ma, Jingtang Li","doi":"10.1007/s10142-025-01649-3","DOIUrl":"10.1007/s10142-025-01649-3","url":null,"abstract":"<p><p>Fish collagen is gaining increasing attention in tissue engineering due to its exceptional bioactivity. This study aimed to isolate functional fish collagen fragments capable of microbial biosynthesis and supporting bone tissue regeneration. Collagen fragments of 150 amino acids were extracted from Cyprinus carpio collagen I (CcCOL1), and their bioactivity, net charge, and hydrophobicity were calculated and analyzed for correlations, these physicochemical and sequential features were using to train the machine learning model, which classified the fragments into three subgroups. Representative samples were selected from each cluster or directly from the original CcCOL1. Six out of eight variants were successfully secreted in Pichia pastoris, and all formed triple-helical structures, while only Var-2 and Var-3 retained self-assembly at 15 °C. Notably, Var-2 exhibited the highest capacity to induce osteoblast differentiation. To develop scaffolds with enhanced mechanical strength, Var-2 was combined with chitin and hydroxyapatite (HAP). The resulting composite demonstrated a compressive strength of 5.77 ± 0.32 MPa while maintaining high porosity at a chitin-HAP ratio of 2:1. Cytotoxicity assays confirmed biocompatibility, and fibroblast differentiation was comparable to Var-2 alone. In vivo rat tibia defect studies showed significant bone regeneration after 12 weeks, highlighting the potential of this fish collagen-chitin-HAP biomaterial for bone tissue engineering.</p>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":"145"},"PeriodicalIF":3.9,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558735","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":"iACP-DPNet: a dual-pooling causal dilated convolutional network for interpretable anticancer peptide identification.","authors":"Zimeng Zhang, Xin Wang, Wenhui Shang","doi":"10.1007/s10142-025-01641-x","DOIUrl":"https://doi.org/10.1007/s10142-025-01641-x","url":null,"abstract":"<p><p>Anticancer peptides (ACPs) are acknowledged for their potential in cancer therapy, attributed to their safety, low side effects, and high target specificity. However, the discovery of ACPs is slowed by the high cost and labor-intensive nature of experimental validation, resulting in a limited number of confirmed ACPs. Although various computational methods have been proposed, existing models commonly suffer from three critical limitations: reliance on small-scale datasets, lack of interpretable feature learning mechanisms, and insufficient generalization capability. To address these challenges, this study constructs a larger and more diverse dataset by consolidating data from existing literature and databases, and proposes a novel deep learning predictive model named iACP-DPNet. The model utilizes the protein language model ProtBert with positional encoding to convert protein sequences into feature vectors, then applies a two-step feature selection process via LightGBM and MIC. The selected features undergo processing by a causal dilated convolution network. A dual-pooling mechanism is designed to enhance the model's ability to synergistically model local critical residues and global sequence contexts, integrating parallel GlobalAveragePooling and attention pooling layers. Compared to traditional single-pooling models (e.g., ACP‑MHCNN), this architecture significantly improves feature extraction capability. To understand the model's decision-making process, we employ t-SNE for visualizing key steps, ISM for interpreting sequence regions, and SHAP analysis for evaluating feature importance. These approaches significantly improve the model's interpretability. The model exhibits outstanding performances on the novel dataset, as evidenced by rigorous tenfold cross-validation. Achieving remarkable metrics-including Sp of 96.1%, Sn of 92.91%, Acc of 94.5% and MCC of 89.05%, it significantly outperforms all existing state-of-the-art methods in comparative analyses. Furthermore, to assess its generalizability, we evaluated iACP-DPNet on an additional dataset, where it outperformed other current models. In conclusion, the iACP-DPNet exhibits exceptional performance and generalizability, showcasing its advanced design and effectiveness in ACPs prediction. This research provides a robust and interpretable framework for advancing research in anticancer peptide discovery. HIGHLIGHTS: • We have established a larger and more diverse dataset for ACPs prediction, addressing the limitations of existing datasets and providing a robust foundation for model training and evaluation. • The implementation of a dual-pooling layer mechanism (GlobalAveragePooling and attention pooling) bolsters the model's capacity to learn diverse features, ultimately enhancing its prediction efficiency. • We employed t-SNE visualization and ISM-based interpretability analysis to provide insights into the model's decision-making process, highlighting key regions and amino acids crit","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":"147"},"PeriodicalIF":3.9,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558736","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}
Ruru Gu, Shuai Li, Bin Yu, Jiaoyang Gu, Bingxin Guan, Honglei Wu
{"title":"Increased CDKN2A expression correlates with resistance to platinum-based therapy and decreased infiltration of B lymphocytes in colon adenocarcinoma.","authors":"Ruru Gu, Shuai Li, Bin Yu, Jiaoyang Gu, Bingxin Guan, Honglei Wu","doi":"10.1007/s10142-025-01657-3","DOIUrl":"https://doi.org/10.1007/s10142-025-01657-3","url":null,"abstract":"<p><strong>Background: </strong>Cuproptosis-related gene CDKN2A is involved in the development and progression of various solid tumors. However, the potential involvement of CDKN2A in colon adenocarcinoma (COAD) remains unexplored.</p><p><strong>Methods: </strong>The expression profiles of cuproptosis-related genes in COAD and their relationships with survival prognosis were analyzed using TCGA and GEO bulk RNA-sequencing datasets. Subsequently, enrichment analysis, genomic mutation analysis, drug sensitivity analysis, and immune infiltration analysis were conducted to assess the significance of CDKN2A in COAD. Using a single-cell RNA-sequencing dataset, we investigated the intercellular communication networks among B lymphocytes according to CDKN2A expression. Furthermore, the potential roles of CDKN2A in COAD were validated through a series of in vitro experiments.</p><p><strong>Results: </strong>CDKN2A was highly expressed in COAD, contributing to platinum resistance through its association with extracellular matrix organization and DNA adduct chemical carcinogenesis. It correlated with the Wnt and Hippo signaling pathway, poor prognosis, and reduced B lymphocyte infiltration, but was not a major oncogenic driver in COAD. Elevated CDKN2A altered the communication patterns between non-switched memory B cells and switched memory B cells. Notably, small interfering RNA-mediated knockdown of CDKN2A in COAD inhibited glycolysis, promoted cuproptosis, and suppressed tumor proliferation, invasion and migration.</p><p><strong>Conclusion: </strong>Our study demonstrated that the cuproptosis-related gene CDKN2A is a promising prognostic biomarker in COAD and may potentially guide the personalized chemotherapy regimens for COAD patients.</p>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":"144"},"PeriodicalIF":3.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551619","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}
Zukela Ruzi, Wei Zha, Huang Yuan Yuan, Jiaorui Liu
{"title":"RNA G-quadruplexes: emerging regulators of gene expression and therapeutic targets.","authors":"Zukela Ruzi, Wei Zha, Huang Yuan Yuan, Jiaorui Liu","doi":"10.1007/s10142-025-01656-4","DOIUrl":"https://doi.org/10.1007/s10142-025-01656-4","url":null,"abstract":"<p><p>RNA G-quadruplexes (rG4s) are non-canonical, four-stranded secondary structures formed by guanine-rich RNA sequences. These dynamic elements have garnered significant attention for their critical roles in regulating gene expression, including translation, alternative splicing, mRNA localization, and stability. This review synthesizes recent progress in understanding the structural determinants and formation dynamics of rG4s, highlighting the contributions of sequence motifs, ionic conditions, and RNA-binding proteins to their stability and function. Functional studies reveal that rG4s modulate key oncogenic transcripts (e.g., MYC, BCL2), contribute to splicing regulation, and influence intracellular RNA trafficking. In pathological contexts, rG4s have been implicated in the molecular etiology of cancers, neurodegenerative diseases such as amyotrophic lateral sclerosis and Fragile X syndrome, and viral replication mechanisms in pathogens including HIV and SARS-CoV-2. Advances in high-throughput techniques, such as G4-seq, rG4-seq, and live-cell imaging, have facilitated the global identification and characterization of rG4s in physiological and disease settings. Moreover, the therapeutic targeting of rG4s using small molecules holds promise for selective gene regulation and biomarker development. Comparative analyses across in vitro, in vivo, and clinical studies underscore the cell-type-specific and context-dependent roles of rG4s, especially in mediating stress responses and apoptosis. Despite methodological limitations and challenges in achieving targeted delivery, rG4s represent a compelling frontier for precision medicine. This review outlines current insights and future directions toward harnessing rG4 biology for therapeutic innovation.</p>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":"143"},"PeriodicalIF":3.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551620","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}
Beena Briget Kuriakose, Ahmed Hjazi, Raed Obaid Saleh, Ashok Kumar Bishoyi, S Renuka Jyothi, Sami G Almalki, G Sridevi, Kamlesh Chaudhary, Ahmed Hussein Zwamel, O Matchonov
{"title":"LncRNAs in hypoxic microenvironment; insight in their impact in cancer biology.","authors":"Beena Briget Kuriakose, Ahmed Hjazi, Raed Obaid Saleh, Ashok Kumar Bishoyi, S Renuka Jyothi, Sami G Almalki, G Sridevi, Kamlesh Chaudhary, Ahmed Hussein Zwamel, O Matchonov","doi":"10.1007/s10142-025-01635-9","DOIUrl":"10.1007/s10142-025-01635-9","url":null,"abstract":"<p><p>Hypoxia may facilitate metastasis and tumor advancement in solid tumors. Intratumoral hypoxia may facilitate tumor aggressiveness by stabilizing hypoxia-inducible factor-1α (HIF-1α). Various transcriptional and epigenetic pathways modulate hypoxia-stimulated gene expression and tumor progression. Noncoding RNAs longer than 200 nt are long noncoding RNAs (lncRNAs). Current lncRNA profiling in several human tumor types revealed that lncRNA expression and deregulation vary by tumor type and may undergo transcriptional, genomic, and epigenetic modifications. LncRNAs controlled by hypoxia have emerged as a prominent focus in hypoxia-regulated biology due to their ability to influence multiple biological procedures associated with tumorigenesis. Hypoxia-regulated lncRNAs may influence tumor development, growth, anti-apoptosis, migration, invasion, angiogenesis, and tumor metabolism. In this light, hypoxia-inducible lncRNAs could interact with protein/protein complex and chromatin/epigenetic factors and another mechanism, thus favoring tumorigenesis. Conversely, lncRNAs may control hypoxia signaling by stabilizing HIF-1α via several mechanisms. Nonetheless, several undiscovered lncRNAs remain that may mediate or regulate the hypoxia axis. Consequently, the novel lncRNAs modulated by hypoxia or that influence hypoxia signaling have yet to be discovered and thoroughly described. Herein, we aim to classify suitable lncRNA targets to offer a feasible therapeutic modality for hypoxia-driven cancers.</p>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":"142"},"PeriodicalIF":3.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537672","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":"Bioinformatics analysis and expression of the transcription factor MYC2 in Brassica napus in response to salt stress.","authors":"Alireza Mirzaei, Jamshid Fooladi, Bahman Fazeli-Nasab, Mansour Ghorbanpour","doi":"10.1007/s10142-025-01647-5","DOIUrl":"https://doi.org/10.1007/s10142-025-01647-5","url":null,"abstract":"<p><p>Salt stress is a significant factor limiting plant growth and can severely reduce crop yields. In addition to causing physiological damage, salt stress disrupts the plant's internal balance and hinders nutrient absorption. However, plants have developed various responses to combat this stress. This study focuses on one critical gene associated with the jasmonic acid pathway, known as BnMYC2, which plays an important role in enhancing salt resistance. The BnMYC2 gene activates downstream genes by binding to specific cis-acting element regions, thereby contributing to the plant's ability to withstand salt stress. We investigated the expression of the BnMYC2 gene in the roots, stems, and leaves of the Licord cultivar under salt stress. The experiment was designed completely randomly, with three replications. Our results indicate that BnMYC2 gene expression is higher in the roots compared to the stems and leaves. Notably, the expression level of the BnMYC2 gene peaked in the roots 12 h after the application of salt stress before subsequently decreasing. Bioinformatics analysis revealed that the BnMYC2 gene shares phylogenetic similarities with 16 genes in Arabidopsis thaliana and 8 genes in Glycine max. Additionally, the expression profile of the MYC2 gene in A. thaliana is 72.22% similar to that in the G. max genome. Overall, this research not only highlights the role of the MYC2 gene in salt tolerance but also provides valuable insights into the evolutionary aspects of the BnMYC2 gene, which can be beneficial for future studies related to genome analysis.</p>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":"141"},"PeriodicalIF":3.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537671","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}
Murshid Muhammed P K, Madhuri C Pagariya, Pritam R Jadhav, Nikita S Gawade, Dipak K Sarode, Suhas Gorakh Karkute, Hemant B Kardile, Rupesh Deshmukh, Suprasanna Penna, Prashant G Kawar
{"title":"Advancing ornamental plant breeding through genomic technologies: opportunities, challenges, and future directions.","authors":"Murshid Muhammed P K, Madhuri C Pagariya, Pritam R Jadhav, Nikita S Gawade, Dipak K Sarode, Suhas Gorakh Karkute, Hemant B Kardile, Rupesh Deshmukh, Suprasanna Penna, Prashant G Kawar","doi":"10.1007/s10142-025-01640-y","DOIUrl":"https://doi.org/10.1007/s10142-025-01640-y","url":null,"abstract":"<p><p>The ornamental plants constitute an important sector of horticulture industry, which are worth billions of dollars worldwide. There is a growing demand for new and improved cultivars and hence, breeders employ new tools and methods to address the problem of plant improvement. Recent advancements in Ornamental plant genomics have seen a great revolution due to new technologies of whole genome sequencing which have created previously unheard-of breeding program prospects. Research into gene regulation, genomic variations, genome evolution, and other biological processes are now aided by the use of complete genome sequencing data. The assembly of high-quality genomes for various ornamental species has facilitated the identification of genes controlling desirable traits such as flower color, shape, fragrance, biotic and abiotic stress resistance. The CRISPR/Cas9 based genome editing technology has offered immense scope for ornamental plant improvement through the enhancement of floral characteristics. Herein, we discuss how these genomic resources can be leveraged to improve breeding efficiency, accelerate the development of novel cultivars to augment the sustainability of the ornamental plant industry. This review aims to provide a viewpoint for the application of whole genome sequencing in ornamental plant breeding, highlighting the opportunities, challenges, and future prospects.</p>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":"140"},"PeriodicalIF":3.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537670","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}
Zhi-Guo Liu, Nan Wang, Wan-Jie Wang, Lei Huang, Shun-Shun Chi, Yu-Xin Nie, Mao-Sha Yuan, Ya-Ru Sun, Yu-Lian Mu, Kui Li
{"title":"Transcriptome analysis reveals no obvious unintended effects in the spleen of CRISPR/Cas9-mediated CD163 and pAPN double-knockout pigs.","authors":"Zhi-Guo Liu, Nan Wang, Wan-Jie Wang, Lei Huang, Shun-Shun Chi, Yu-Xin Nie, Mao-Sha Yuan, Ya-Ru Sun, Yu-Lian Mu, Kui Li","doi":"10.1007/s10142-025-01639-5","DOIUrl":"10.1007/s10142-025-01639-5","url":null,"abstract":"<p><p>Gene editing provides powerful tools for farm animal breeding. Our group previously obtained CD163/pAPN double-knockout (DKO) pigs via CRISPR/Cas9 and somatic cell nuclear transfer. These pigs are not only resistant to three infectious viruses but also maintain normal production performance. However, unintended effects of CRISPR/Cas9 tools may pose potential risks to animal well-being or safety. This study aimed to characterize the differences in splenic gene expression between wild-type (WT) and DKO pigs, providing a basis for safety evaluation of gene-edited animals. A comprehensive transcriptional panorama reflected considerable congruence in the aggregate gene expression profiles of the DKO and WT pigs. Comparisons between 35-day-old and 11-month-old DKO pigs and their WT equivalents revealed 225 and 242 differentially expressed genes (DEGs), respectively, a count significantly lower than that of the DEGs in the disparate developmental stage comparison groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that the majority of DEGs between DKO and WT pigs correlated with the biological functions of CD163 and pAPN, without any alterations in the expression of tumor suppressor genes in DKO pigs. This revealed a less pronounced effect of dual gene editing on the gene expression profile of porcine spleens than the effect of animal maturation, with no evident unanticipated consequences observed in DKO pigs.</p>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":"139"},"PeriodicalIF":3.9,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511393","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}