Functional & Integrative Genomics最新文献

{"title":"Unveiling the Therapeutic Potential of Targeting RRM2 in Hepatocellular Carcinoma: An Integrated In Silico and In Vitro Study.","authors":"Lobna Ibrahim, Rania Hassan Mohamed, Mahmoud M Tolba, Sara M Radwan, Nadia M Hamdy, Mahmoud Elhefnawi","doi":"10.1007/s10142-025-01630-0","DOIUrl":"10.1007/s10142-025-01630-0","url":null,"abstract":"","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":"123"},"PeriodicalIF":3.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257059","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":"Integrated muti-omics data and machine learning reveal CD151 as a key biomarker inducing chemoresistance in metabolic syndrome-related early-onset left-sided colorectal cancer.","authors":"Yingdong Hou, Hubin Xia, Chenshan Xu, Yuhua Yu, Chenghao Ji, Wenli Ruan, Wencheng Kong, Yifeng Zhou, Xiaofeng Zhang","doi":"10.1007/s10142-025-01634-w","DOIUrl":"10.1007/s10142-025-01634-w","url":null,"abstract":"<p><p>Emerging evidence has suggested a potential pathological association between early-onset left-sided colorectal cancer (EOLCC) and metabolic syndrome (MetS). However, the underlying genetic and molecular mechanisms remain insufficiently elucidated. This study aimed to identify and characterize key biomarkers associated with the progression and treatment response of MetS-related EOLCC. An in-hospital cohort was utilized to assess the clinical implications of primary tumor location in early-onset colorectal cancer (EOCRC). Differentially expressed genes (DEGs) and weighted gene coexpression network analysis (WGCNA) were employed to identify genes potentially associated with MetS-related EOLCC. Functional enrichment analyses were conducted to explore the underlying mechanisms. Candidate biomarkers were screened using random forest (RF) and support vector machine-recursive feature elimination (SVM-RFE) algorithms. Survival relevance, expression profiles, and diagnostic performance were analyzed to identify key biomarkers. Treatment responses were evaluated, and potential therapeutic compounds were identified through molecular docking. Single-cell RNA sequencing (scRNA-seq) data and in vitro experiments were used to validate gene expression and functional characteristics. The in-hospital cohort revealed a higher proportion of EOLCC among EOCRC patients. Using the edgeR package and WGCNA, we identified coexpressed genes common to both EOLCC and MetS, significantly enriched in pathways associated with stromal remodeling and metabolic regulation. Machine learning algorithms highlighted three candidate biomarkers. Among them, only CD151 was associated with prognosis and advanced disease stage. CD151 was strongly correlated with stromal remodeling and chemoresistance. Additionally, potential therapeutic compounds targeting MetS-related EOLCC were identified via molecular docking. scRNA-seq analysis confirmed the expression and functional patterns of CD151, particularly in tumor cells. The bioinformatics results were further validated through quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemical (IHC) staining. This study identified CD151 as a key biomarker in MetS-related EOLCC, offering valuable insights into prognosis, tumor biology, and personalized treatment strategies. CD151 may serve as a reference for future research and clinical applications targeting this disease subtype.</p>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":"122"},"PeriodicalIF":3.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245577","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":"PIN1 serves as a prognostic and therapeutic biomarker in lung adenocarcinoma.","authors":"Juncheng Yu, Xiao Lu, Dong Zhou, Jiao Zhang, Xufeng Deng, Xiaobing Liu, Kai Wang, Shuangqing Liao, Hong Zheng, Jigang Dai","doi":"10.1007/s10142-025-01629-7","DOIUrl":"https://doi.org/10.1007/s10142-025-01629-7","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality worldwide, with limited response rates and resistance to targeted therapies and immunotherapies. Pin1, a phosphorylation-specific peptidyl-prolyl isomerase, has been implicated in multiple oncogenic pathways; however, its role in LUAD is not fully understood. We conducted an integrative analysis using public datasets (TCGA, GEO, HPA), LUAD tissue microarrays, malignant pulmonary nodule specimens, and cell line models to investigate the expression and function of PIN1 in LUAD. Functional assays, immunohistochemistry, and in vivo xenograft models were employed to validate the biological effects of PIN1 in LUAD progression and treatment response. PIN1 expression was significantly downregulated in LUAD tissues compared to adjacent normal lung tissues. High PIN1 expression was associated with improved overall survival, increased immune cell infiltration, and enhanced response to immunotherapy. Overexpression of PIN1 inhibited proliferation and migration while promoting apoptosis of LUAD cells in vitro and in vivo. Mechanistically, high PIN1 expression activated downstream pAKT and pMAPK signaling, potentially contributing to EGFR-TKI resistance despite unchanged pEGFR levels. Moreover, functional enrichment analysis and immune profiling revealed that PIN1 is positively associated with antitumor immune responses in LUAD, contrasting its immunosuppressive role in other cancers. PIN1 exhibits tumor-suppressive activity in LUAD and may serve as a promising biomarker for prognosis and therapeutic response. These findings underscore the context-dependent role of PIN1 and support further exploration of its mechanistic involvement in LUAD immunobiology and targeted therapy resistance.</p>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":"121"},"PeriodicalIF":3.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144232901","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":"BIRC5 as a master regulator in HCC: unraveling its role in tumor survival and therapeutic potential.","authors":"Aya M Ayoub, Elham Abdel-Badiea Mahmoud, Rania Hassan Mohamed, Mahmoud M Tolba, Nahla S Hassan, Mohamed Ghazy, Mahmoud ElHefnawi","doi":"10.1007/s10142-025-01615-z","DOIUrl":"10.1007/s10142-025-01615-z","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal malignancies worldwide, with limited effective therapeutic options. Identifying novel targets is crucial for improving treatment strategies. In this study, we integrated bioinformatics and experimental approaches to uncover key regulatory genes in HCC. BIRC5 (survivin) emerged as a central hub gene, playing a pivotal role in apoptosis inhibition and cell cycle regulation. Using CRISPR-Cas9-mediated knockout in HepG2 cells, we demonstrated that BIRC5 depletion significantly suppressed cell proliferation and migration while inducing apoptosis. Furthermore, BIRC5 knockout led to cell cycle arrest, cytokinesis defects, and autophagy activation, highlighting its essential role in tumor maintenance. Functional assays, including colony formation, wound healing, flow cytometry, gene expression profiling, and transmission electron microscopy, validated these findings. Notably, the downregulation of key oncogenic pathways, including PI3K and AURKA, underscores the critical function of BIRC5 in sustaining HCC cell survival and proliferation. These results position BIRC5 as a promising therapeutic target, with the potential to disrupt tumor growth and metastasis. Targeting BIRC5 could offer a novel strategy for improving HCC treatment outcomes, paving the way for more effective therapeutic interventions against this aggressive cancer.</p>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":"120"},"PeriodicalIF":3.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223965","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":"Analyzing the potential targets and mechanism of per- and polyfluoroalkyl substances (PFAS) on breast cancer by integrating network toxicology, single-cell sequencing, spatial transcriptomics, and molecular simulation.","authors":"Jiajun Li, Deqi Wang, Sihan Song, Yi Wang, Xinlei Wu, Zhuoyi Du, Yanggang Hong","doi":"10.1007/s10142-025-01616-y","DOIUrl":"https://doi.org/10.1007/s10142-025-01616-y","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS), particularly perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are persistent environmental contaminants linked to adverse health effects, including an increased risk of breast cancer. However, the molecular mechanisms through which PFAS contribute to breast cancer development remain poorly understood. In this study, we employed an integrated approach combining network toxicology, single-cell sequencing, spatial transcriptomics, and molecular simulation to investigate the effects of PFAS on breast cancer. By constructing a protein-protein interaction (PPI) network, we identified six core genes (PPARG, CD36, FABP4, PPARGC1A, LPL, and PCK1) that play a significant role in the development of breast cancer. These genes are involved in key cellular processes such as lipid metabolism, oxidative phosphorylation, and immune regulation, all of which are disrupted by PFAS exposure. Single-cell and spatial transcriptomic analyses revealed that these genes are predominantly expressed in endothelial, myeloid, and cancer-associated fibroblasts within the tumor microenvironment. Molecular simulation further confirmed strong binding energies between PFAS and these target proteins, suggesting direct interactions. Our findings provide novel insights into how PFAS may promote breast cancer progression at the molecular level and highlight the need for further research on environmental pollutants in cancer risk assessment and public health initiatives.</p>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":"119"},"PeriodicalIF":3.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214577","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":"Selenium deficiency is functionally linked with the molecular etiopathogenesis of necrotizing enterocolitis (NEC).","authors":"Kubilay Gürünlüoğlu, Muhammed Dündar, Turgay Ünver, Hatice Turgut, Semra Gürünlüoğlu, Necmettin Akpınar, Hasan Ateş, Ramazan Özdemir, Turan Yıldız, Mehmet Demircan, Mehmet Aslan, Ahmet Koç","doi":"10.1007/s10142-025-01628-8","DOIUrl":"10.1007/s10142-025-01628-8","url":null,"abstract":"<p><p>Necrotizing enterocolitis (NEC) is a severe and often catastrophic gastrointestinal emergency that predominantly affects neonates, especially those born prematurely, and is associated with high rates of morbidity and mortality. Despite its significant clinical impact, the precise etiology and molecular pathogenesis of NEC remain incompletely understood. In this study, we conducted global transcriptomic profiling using high-throughput RNA sequencing in 11 premature neonates diagnosed with NEC, following rigorous inclusion and exclusion criteria. Compared to healthy controls, we identified 1,204 differentially expressed genes (DEGs), including 636 upregulated and 568 downregulated transcripts. Notably, genes involved in hypoxia-induced apoptosis (e.g., HIF1 AAS3, HIF1 AAS1), the caspase cascade (BCL2, BCL6, CASP5, CASP7), and inflammation (IL1RAP, IL6ST, TNFAIP3, TNFRSF10 A, TLR6, TLR10) were significantly upregulated. In contrast, IL18, a key modulator of inflammatory responses, was downregulated. Interestingly, several genes encoding selenoproteins (GPX1, GPX4, SELENON, SELENOM, SELENOF, SELENOW, SELENOT) were also downregulated, suggesting molecular evidence of selenium deficiency. Gene ontology and pathway enrichment analyses revealed widespread dysregulation in pathways related to hypoxia response, systemic inflammation, coagulation, antimicrobial defense, mitochondrial function, autophagy, selenium metabolism, and apoptosis. Collectively, our findings provide novel insights into the molecular underpinnings of NEC in premature infants and suggest that systemic hypoxia, oxidative stress, selenium deficiency, and programmed cell death contribute significantly to its pathogenesis.</p>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":"118"},"PeriodicalIF":3.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12134042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207339","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":"A novel oncogene, leucine-rich repeat protein 1, mediates hypoxia-induced hepatocellular carcinoma progression.","authors":"Li Tao, Yixian Guo, Runkun Liu, Meng Lv, Yufeng Wang","doi":"10.1007/s10142-025-01626-w","DOIUrl":"https://doi.org/10.1007/s10142-025-01626-w","url":null,"abstract":"<p><p>The involvement of leucine rich repeats protein 1 (LRR1) in various biological processes has been established, but its specific role and potential mechanisms in hepatocellular carcinoma (HCC) remain unclear. The aim of this study was to explore the potential expression, function, and mechanisms of LRR1 in HCC. Data acquired from TCGA, GEO and other online databases was used to investigate the expression and roles of LRR1 in HCC through various approaches, including expression profiling, clinical significance analysis, methylation status examination, immune infiltration assessment, genomic mutation analysis, and pathway network exploration. With findings in bioinformatic analysis, we further validated the involvement of LRR1 in HCC progression by cellular experiments. The expression of LRR1 is significantly upregulated in HCC compared to normal liver tissues and cell line. Additionally, the involvement of LRR1 was implicated in various modifications across diverse aspects associated with HCC. Enrichment analysis indicated that LRR1 was induced by hypoxia in HIF-1-dependent manner. The cell experiments convincingly demonstrated the pivotal role of LRR1 in tumor cell proliferation, migration, invasion and angiogenesis under the regulation of HIF-1. Our findings demonstrate a novel oncogene LRR1 in HCC, which is also a HIF-1 target gene and functions as a promising biomarker and contributes to the hypoxia-induced progression of HCC through a HIF-1/LRR1 manner.</p>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":"117"},"PeriodicalIF":3.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207338","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":"An efficient hairy root system for validation of CRISPR/Cas system activities in cotton.","authors":"Manyu Zhang, Lili Zhou, Mahideen Afridi, Huiming Guo, Hongmei Cheng","doi":"10.1007/s10142-025-01627-9","DOIUrl":"https://doi.org/10.1007/s10142-025-01627-9","url":null,"abstract":"<p><p>The hairy root induction system has been widely applied in studying gene expression and function in plant species due to its rapidity and efficiency. The hairy root system is an efficient tool for evaluating the activities of CRISPR/Cas systems. Cotton hairy roots were primarily induced through cotton tissue culture under aseptic conditions and by injecting cotton stem tips under non-aseptic conditions. However, both methods are lab-intensive and time-consuming. In this study, an efficient cotton hairy root induction procedure was established via infecting cotton hypocotyls with Agrobacterium rhizogenes under non-sterile conditions. Cotton seedlings with expanded cotyledons were decapitated with a slanted cut, and the residual hypocotyl (maintained 1 cm apical portion) was inoculated with A. rhizogenes. Over 90% of the infected explants from all three tested varieties could produce hairy roots after 8 days of inoculation. The effictiveness of the method was tested by overexpressing two reporter genes (eGFP and GUS). The transformation efficiency of the GUS and eGFP were ranged from50-68.18% and 40.9-68.18%. In addition, the editing efficiency of target sites in different CRISPR/Cas systems were also tested in hairy root. This method provided technical support for screening suitable target sites for cotton gene editing.</p>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":"116"},"PeriodicalIF":3.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197975","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":"Functional genomics reveals adipose-kidney crosstalk as a contributor to kidney fibrosis via the OSM-OSMR pathway.","authors":"Jing Zhang, Zhaojun Liu, Shihui Dong, Kun Xu, Kangchun Wang, Luyu Gong, Qiaoqiao Liu, Yue Guo, Yeping Zhu, Jingrong She, Song Jiang, Shaolin Shi, Zhihong Liu, Jingping Yang","doi":"10.1007/s10142-025-01624-y","DOIUrl":"https://doi.org/10.1007/s10142-025-01624-y","url":null,"abstract":"<p><p>Kidney injury is a severe complication of type 2 diabetes, yet its pathophysiology varies among patients. Although abnormal adipose has been identified as an indicator for the risk of kidney injury in type 2 diabetes, the underlying mechanisms remain unclear. Here, we integrated adipose functional genomics and genome-wide association studies of diabetic nephropathy (DN) to investigate the relationship between adipose and kidney injury. By generating the epigenome, transcriptome and regulatome, we constructed functional genomics map of adipose, revealing the regulatory role of perirenal adipose tissue in kidney disease. Integration of the functional genomics with genetic risk demonstrated that the genetic risk of DN is mediated not only through the kidney itself but also via adipose-kidney crosstalk. Our results revealed that risk variant rs2412980 functions through an adipose-specific regulatory element to control the expression of OSM, encoding the cytokine oncostatin-M. Adipose-derived OSM can reprogram OSMR-expressing renal fibroblasts, and subsequent activation of OSM-OSMR pathway is associated with advanced kidney injury, including reduced eGFR, elevated proteinuria and creatinine levels. Our work confirmed the linkage between adipose and kidney diseases with the genetic evidence, and revealed that the adipo-renal axis promotes the fibrosis of kidney under diabetes through the OSM-OSMR pathway.</p>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":"114"},"PeriodicalIF":3.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197976","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":"LSINCT5: a pivotal oncogenic long non-coding RNA in cancers.","authors":"Sharanya K Sritharan, Amar Harris Arifin, Shamala Salvamani, Rhun Yian Koh, Baskaran Gunasekaran","doi":"10.1007/s10142-025-01610-4","DOIUrl":"https://doi.org/10.1007/s10142-025-01610-4","url":null,"abstract":"<p><p>Long stress-induced non-coding transcript 5 (LSINCT5) is a long non-coding RNA (lncRNA) that has been demonstrated to exhibit oncogenic properties as its upregulation was found to be commonly associated with malignant clinicopathological features in various cancers. Numerous studies have reported that LSINCT5 overexpression may promote cancer progression by regulating the expression of genes that modulate important aspects of cell activity and by interfering with signalling pathways via precise mechanisms such as microRNA (miRNA) sponging, protein interactions, as well as acting as a downstream target of transcription factors. Eventually, these processes stimulate malignant behaviour such as proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT). Research suggests LSINCT5 could be a useful biomarker and therapeutic target. However, understanding their complex nature and impact on physiological processes is crucial for determining their oncogenic properties and potential use in therapy. This review focuses on LSINCT5's biological functions, expression patterns, oncogenic roles, and molecular mechanisms in cancers. We further highlight the potential of LSINCT5 as a biomarker for early diagnosis and prognosis, as well as a therapeutic target in cancer therapy.</p>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":"115"},"PeriodicalIF":3.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197977","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}