Genes & genomics最新文献

{"title":"The GPR4 antagonist NE 52-QQ57 prevents ox-LDL-induced cellular senescence by promoting the expression of SIRT1.","authors":"Wei Luo, Jiming Zhou, Feng Liang, Xianghui Chou, Zhengliang Peng, Weihua Tan, Ziying Yu, Huan Wan","doi":"10.1007/s13258-024-01610-x","DOIUrl":"https://doi.org/10.1007/s13258-024-01610-x","url":null,"abstract":"<p><strong>Background: </strong>Cell senescence-associated endothelia dysfunction is a vital point in the pathological progression of atherosclerosis (AS). G-protein coupled receptor 4 (GPR4) is a proton-sensing receptor involved in developing endothelial dysfunction.</p><p><strong>Objective: </strong>In this study, we investigated the protective role of NE 52-QQ57, a GPR4 inhibitor in endothelial cell senescence induced using an oxidized low-density lipoprotein (ox-LDL). We also unravel the underlying molecular mechanism of NE 52-QQ57 as a therapeutic agent.</p><p><strong>Methods: </strong>Endothelial cell senescence model was established using human aortic endothelial cells (HAECs) stimulated with ox-LDL. The expression levels of GPR4, p53, p16, and sirtuin1 (SIRT1) were evaluated using real-time PCR and western blot assays. ROS production was determined using dihydroethidium (DHE) staining. Further, interleukin-6 (IL-6) and monocyte chemotactic protein 1 (MCP-1) secretion and expression were determined using ELISA and real-time PCR analysis, respectively. Finally, β-galactosidase (SA-β-Gal) staining associated with cell senescence, telomerase activity, and cell cycle assay were used to determine the state of cell senescence.</p><p><strong>Results: </strong>Firstly, GPR4 was found to be upregulated in the ox-LDL-stimulated HAECs. We also identified elevated ROS, IL-6, and MCP-1 levels induced by ox-LDL and significantly abrogated by NE 52-QQ57 treatment. Second, a reversal in SA-β-Gal activity, telomerase activity, and G0/G1 proportion, with an upregulation in p53 and p16 expressions was observed on NE 52-QQ57 treatment in the ox-LDL induced model. Lastly, the decreased expression level of SIRT1 was extremely elevated by NE 52-QQ57. Notably, the inhibitory effect of NE 52-QQ57 against ox-LDL-induced cell senescence was abolished by the SIRT1 inhibitor EX-527.</p><p><strong>Conclusion: </strong>The GPR4 antagonist NE 52-QQ57 might prevent cellular senescence by promoting the expression of SIRT1.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965207","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":"RalB promotes lymph node metastasis in tongue squamous cell carcinoma.","authors":"Yuman Zhang, Jiali Yang, Yi Gong, Zhihan Liu, Yanguang Yang, Xiaoyong Song, Yuting Gao, Yajun Xiong, Dan Wang, Kai Fu, Lifeng Jia, Xinli Shi","doi":"10.1007/s13258-025-01628-9","DOIUrl":"https://doi.org/10.1007/s13258-025-01628-9","url":null,"abstract":"<p><strong>Background: </strong>Lymph nodes metastasis is the main metastasis mode of tongue squamous cell carcinoma (TSCC). Ras related GTP binding protein B (RalB) have been recently described that it was involved in tumor growth and metastasis, but the effect in TSCC is still ill-defined.</p><p><strong>Objective: </strong>This study provides insights into the role of RALB as a prognostic factor in head and neck squamous cell carcinoma (HNSCC) and demonstrates its involvement in promoting lymph node metastasis in TSCC.</p><p><strong>Methods: </strong>Firstly, the expression level of RALB and the relationship with clinical features were examined. Subsequently, RALB knockdown Cal-27 cells orthotopic xenotransplantation in the tongue of BALB/c nude mice were established. Finally, using Connectivity Map (CMAP) database to find possible drugs.</p><p><strong>Results: </strong>Firstly, RALB could not only predict the cancer patients' prognosis and survival and but also act as a potential prognostic factor, particularly in HNSCC by pan-cancer bioinformatics analysis. In addition, we found that RalB promoted tumor growth and lymph node metastasis. Finally, we identified Tirabrutinib (ONO-4059) targeting RalB with good binding properties.</p><p><strong>Conclusions: </strong>RalB act as a prognostic gene in HNSCC, and promote lymph node metastasis in early stage of TSCC.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992651","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":"Transcriptomic analysis revealed that short-day treatment of seedlings promotes flowering in maize (Zea mays L.).","authors":"Chunlei Li, Hongquan Mao, Xiaoxue Fan, Meihui Yu, Xiaoming Yu","doi":"10.1007/s13258-025-01640-z","DOIUrl":"https://doi.org/10.1007/s13258-025-01640-z","url":null,"abstract":"<p><strong>Background: </strong>In this study, blockage of transition from vegetative to reproductive growth was observed in short-day maize (Zea mays L.) varieties under long-day conditions.</p><p><strong>Methods: </strong>Two short-day varieties, namely, CML116 and CML493, were cultivated under long-day conditions at various time points of short-day treatments of seedlings. Notably, short-day treatment was started at the three-leaf stage and ended at the five- (5 L), seven- (7 L) and nine-leaf (9 L) stages. Moreover, transcriptomic analysis (RNA-seq) was carried out to examine the gene expression profiles.</p><p><strong>Results: </strong>The results of gene functional analysis showed that DEGs related to light stimulation and circadian rhythm had different expression patterns among various groups. Additionally, ZmCO, ZmSOC1, ZmFT and ZmHY5 acted as the key regulators of the transition process from vegetative to reproductive growth. Furthermore, the expression of most CO transcripts reached a peak at 5 L in both CML493 and CML116 but decreased in the subsequent short-day treatment.</p><p><strong>Conclusions: </strong>It is possible that accumulation of CO and FT at the seedling stage facilitated transition from vegetative to reproductive growth. In addition, long-day conditions were not conducive to the accumulation of CO and FT as well as their downstream target, SOC1. Moreover, accumulation of the HY5 protein promoted photomorphogenesis, which played a positive role in promoting the normal development of maize plants.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794731","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 identification of NAC transcription factors in Acer paxii, and their expression dynamics during leaf aging.","authors":"Yuzhi Fei, Shah Faheem Afzal, Zhu Chen, Yue Zhao, Xin Meng, Jie Ren, Shuiming Zhang","doi":"10.1007/s13258-025-01638-7","DOIUrl":"https://doi.org/10.1007/s13258-025-01638-7","url":null,"abstract":"<p><strong>Background: </strong>The NAC family (consisting of NAM, ATAF1/2, and CUC2) represents a crucial plant-specific transcription factor family, contributing significantly to various aspects of plant growth, development, and reactions to abiotic stresses. Yet, the underlying mechanism of NAC regulation in Acer paxii has not been discussed.</p><p><strong>Objectives: </strong>Identification of NAC genes (ApNACs) in the genome of Acer paxii and exploring the regulatory network of NACs in mediating leaf senescence.</p><p><strong>Methods: </strong>A thorough genome-wide analysis of the NAC gene family in the Acer paxii genome was performed.</p><p><strong>Results: </strong>We identified 117 ApNACs from the Acer paxii genome database, which were irregularly distributed across 13 chromosomes. Phylogenetic analysis revealed that ApNAC genes were partitioned into 16 subgroups. There are four kinds of cis-regulatory elements in the promoter region of the ApNACs gene. We compared the expression levels of ApNAC genes at different times using transcriptome data and selected six ApNAC genes for qRT-PCR, which the results showed basic consistency with the transcriptome results. Six ApNACs and 187 TFs from different families were selected, and it was found that the TF families with the highest correlation were WRKY, MYB, bZIP, and ERF, and these TF families were reported to participate in the regulation function in senescence.</p><p><strong>Conclusion: </strong>This study provides important data support for identifying the NAC gene family of Acer paxii and the regulatory function of the ApNAC genes on plant senescence, which will help to understand the NAC-mediated regulatory network in Acer paxii.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752374","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":"BRN3A, a transcription factor, regulates the expression of genes involved in biological processes shaping the HPV induced cervical cancer.","authors":"Anand Prakash, Yashvant Patel, Jagat Kumar Roy","doi":"10.1007/s13258-025-01620-3","DOIUrl":"10.1007/s13258-025-01620-3","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer is the fourth most common cancer worldwide in females. This occurs primarily due to the infection of high-risk Human Papilloma Virus (HPV), although in advanced stages it requires support from host cellular factors. BRN3A is one such host cellular factors, whose expression remains high in cervical cancers and upregulates tumorigenic HPV gene expression. The effect of BRN3A on HPV-mediated cervical cancer and the underlying mechanism remains obscure.</p><p><strong>Objective: </strong>To investigates the effect of BRN3A on cancer-promoting biological processes in HPV-positive uterine cervix cancer cells.</p><p><strong>Methods: </strong>We have altered the expression of BRN3A through over-expression (OE) and knock-down (KD) constructs in cervical cancer cell line, SiHa, and did transcriptome profiling through next-generation RNA-sequencing, validation through RT-PCR and BRN3A binding study with in silico promoter study and ChIP PCR methods.</p><p><strong>Results: </strong>This study revealed a substantial change in the expression of several genes associated with cancer-promoting biological processes including viral processes, immune response, cell-death, cell-proliferation, different signaling pathways, etc. Additionally, promoter analysis through in silico mode revealed that a total of 32.7% of genes possess BRN3A binding sites at their promoters. Physical interaction of BRN3A with IFITM1, OAS3, ISG15, BCL2L1 and HSP90AB1 genes was also confirmed.</p><p><strong>Conclusions: </strong>The present study identified molecular targets of BRN3A and provided new insight into the pathogenesis of cervical cancer. According to our knowledge, this is the first report on the effect on eukaryotic transcriptomes after over-expression and knocking down BRN3A.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"487-501"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052225","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":"A novel CLRN2 variant: expanding the mutation spectrum and its critical role in isolated hearing impairment.","authors":"Farooq Ahmad, Arif Mahmood, Ibrahim Abdullah Almazni, Afnan Mohammed Shakoori, Fatemah Alhakami, Qamre Alam, Muhammad Ismail, Muhammad Umair","doi":"10.1007/s13258-024-01590-y","DOIUrl":"10.1007/s13258-024-01590-y","url":null,"abstract":"<p><strong>Background: </strong>Biallelic variants in the CLRN2 gene have been reported to cause autosomal recessive profound hearing impairment in humans. CLRN2 belongs to the clarin gene family that encodes a tetraspan protein that contains a cytosolic N-terminus, multiple helical transmembrane domains, and an endoplasmic reticulum membrane retention signal, TKGH, in the C-terminus. The encoded protein may be important in development and homeostasis of the inner ear and retina.</p><p><strong>Methods: </strong>Here, we present a consanguineous family suffering from autosomal recessive non-syndromic profound hearing impairment (HI). We employed state of the art Whole exome sequencing (WES), Sanger sequencing followed by routine bioinformatics filtration steps and homology modeling to elucidate the effect of mutation at the protein level.</p><p><strong>Results: </strong>ES followed by Sanger sequencing revealed a novel homozygous nonsense variant in the CLRN2 gene [c.414 C > A; p.Cys138*]. Furthermore, insilico protein modeling of the wildtype and mutated version of the CLRN2 protein revealed large-scale changes that predict to compromise the routine normal function of the protein.</p><p><strong>Conclusion: </strong>Our finding further extends the mutations spectrum of CLRN2 gene and confirms its important role in hearing homeostasis and with developmental disorder in humans.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"417-423"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498909","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":"Advances in cancer genomics and precision oncology.","authors":"Yonjong Heo, Woo-Jin Kim, Yong-Joon Cho, Jae-Won Jung, Nam-Soo Kim, Ik-Young Choi","doi":"10.1007/s13258-024-01614-7","DOIUrl":"10.1007/s13258-024-01614-7","url":null,"abstract":"<p><strong>Background: </strong>Next-generation sequencing has revolutionized genome science over the last two decades. Indeed, the wealth of sequence information on our genome has deepened our understanding on cancer. Cancer is a genetic disease caused by genetic or epigenetic alternations that affect the expression of genes that control cell functions, particularly cell growth and division. Utilization of next-generation sequencing in cancer gene panels has enabled the identification of actionable gene alterations in cancer patients to guide personalized precision medicine.</p><p><strong>Objective: </strong>The aim is to provide information that can identify actionable gene alterations, enabling personalized precision medicine for cancer patients.</p><p><strong>Results & discussion: </strong>Equipped with next-generation sequencing techniques, international collaboration programs on cancer genomics have identified numerous mutations, gene fusions, microsatellite variations, copy number variations, and epigenetics changes that promote the transformation of normal cells into tumors. Cancer classification has traditionally been based on cell type or tissue-of-origin and the morphological characteristics of the cancer. However, interactive genomic analyses have currently reclassified cancers based on systemic molecular-based taxonomy. Although all cancer-causing genes and mechanisms have yet to be completely understood or identified, personalized or precision medicine is now currently possible for some forms of cancer. Unlike the \"one-size-fits-all\" approach of traditional medicine, precision medicine allows for customized or personalized treatment based on genomic information.</p><p><strong>Conclusion: </strong>Despite the availability of numerous cancer gene panels, technological innovation in genomics and expansion of knowledge on the cancer genome will allow precision oncology to manage even more types of cancers.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"399-416"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028557","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 analysis of genetic variability and functional traits in lung adenocarcinoma epithelial cells via single-cell RNA sequencing, GWAS, bayesian deconvolution, and machine learning.","authors":"Chenggen Gao, Jintao Wu, Fangyan Zhong, Xianxin Yang, Hanwen Liu, Junming Lai, Jing Cai, Weimin Mao, Huijuan Xu","doi":"10.1007/s13258-025-01621-2","DOIUrl":"10.1007/s13258-025-01621-2","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma remains a leading cause of cancer-related mortality worldwide, characterized by high genetic and cellular heterogeneity, especially within the tumor microenvironment.</p><p><strong>Objective: </strong>This study integrates single-cell RNA sequencing (scRNA-seq) with genome-wide association studies (GWAS) using Bayesian deconvolution and machine learning techniques to unravel the genetic and functional complexity of lung adenocarcinoma epithelial cells.</p><p><strong>Methods: </strong>We performed scRNA-seq and GWAS analysis to identify critical cell populations affected by genetic variations. Bayesian deconvolution and machine learning techniques were applied to investigate tumor progression, prognosis, and immune-epithelial cell interactions, particularly focusing on immune checkpoint markers such as PD-L1 and CTLA-4.</p><p><strong>Results: </strong>Our analysis highlights the importance of genes like SLC2A1, which regulates glucose metabolism and correlates with tumor invasiveness and poor prognosis. Immune-epithelial interactions suggest a suppressive tumor microenvironment, potentially hindering immune responses. Additionally, machine learning models identify core prognostic genes such as F12, GOLM1, and S100P, which are significantly associated with patient survival.</p><p><strong>Conclusions: </strong>This comprehensive approach provides novel insights into lung adenocarcinoma biology, emphasizing the role of genetic and immune factors in tumor progression. The findings support the development of personalized therapeutic strategies targeting both tumor cells and the immune microenvironment.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"435-468"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12000210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482886","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":"Plant cross-fertilization for production of dual-specific antibodies targeting both Ebola virus-like particles and HER2 protein in F₁ plants.","authors":"Daehwan Lee, Hyunjoo Hwang, Yerin Kim, Yejin Hwang, Keunbeom Youk, Peter Hinterdorfer, Mikyung Kim, Kisung Ko","doi":"10.1007/s13258-025-01616-z","DOIUrl":"10.1007/s13258-025-01616-z","url":null,"abstract":"<p><strong>Background: </strong>This study explores the cross-fertilization of transgenic tobacco plants to produce dual-specific monoclonal antibodies (mAbs) targeting Ebola virus-like particles and HER2 proteins. We generated F₁ plants by hybridizing individual transgenic lines expressing the anti-HER2 breast cancer VHH mAb (HV) and the H-13F6 human anti-Ebola large single chain mAb (EL).</p><p><strong>Objective: </strong>Hybridizing transgenic plants to express dual-antibodies between different structures VHH and LSCK indicate the potential of transgenic plants as a cost-effective and scalable production system for dual targeting mAbs.</p><p><strong>Methods: </strong>We performed polymerase chain reaction (PCR) analysis to confirm the integration of EL and HV genes in the F₁ progeny. The reverse-transcription (RT)-PCR and immunoblotting were performed to confirm the expression of transgenes. Indirect enzyme-linked immunosorbent assay was conducted to confirm the functionality of purified EL and HV mAb.</p><p><strong>Results: </strong>A PCR analysis confirmed the successful integration of both EL and HV mAb genes in the F₁ progeny. Additionally, (RT)-PCR and immunoblotting validated the expression of these transgenes, with EL and HV mAbs purified from the F₁ plants. Indirect enzyme-linked immunosorbent assay (ELISA) demonstrated that EL × HV mAb proteins maintained binding activity to Ebola virus-specific antigens, comparable to that of the EL mAb protein, while also exhibiting binding activity against HER2 proteins similar to that of the HV mAb.</p><p><strong>Conclusion: </strong>This study indicates the potential for transgenic plants to produce dually targeting mAbs, suggesting a promising application in enabling the co-expression of antibodies targeting two different diseases in a single plant.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"425-433"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028599","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":"Comprehensive assessment of the significance of cellular senescence-associated genes in neuroblastoma.","authors":"Yahui Han, Biyun Li, Xiaokun Yu, Jianing Liu, Menghui Zhang, Wei Zhao, Da Zhang, Jiao Zhang","doi":"10.1007/s13258-025-01619-w","DOIUrl":"10.1007/s13258-025-01619-w","url":null,"abstract":"<p><strong>Background: </strong>The clinical course of high-risk neuroblastoma patients remains suboptimal, and the dynamic and reversible nature of cellular senescence provides an opportunity to develop new therapies.</p><p><strong>Objective: </strong>This study aims to identify unique markers of cellular senescence in neuroblastoma and to explore their clinical significance.</p><p><strong>Methods: </strong>The impact of multiple genetic regulatory mechanisms on cellular senescence-associated genes (CSAGs) was first assessed. We identified cellular senescence-associated subtypes by hierarchical clustering and explored the intrinsic differences between subtypes. We screened key CSAGs based on PPI networks and clinical significance. Subsequently, we constructed the cellular senescence-related risk score (CSRS) by LASSO regression and stepwise Cox regression, and validated its performance and stability through multiple methods. Finally, we performed single-cell analysis and constructed the nomogram.</p><p><strong>Results: </strong>The expression of CSAGs was influenced by copy number variation and DNA methylation. We found that significant differences between cellular senescence-associated subtypes in immune infiltration and overall prognosis. AURKA, CDK4, TERT were key genes in the cellular senescence process. CSRS showed superior and robust predictive performance in several cohorts and could serve as an independent prognostic factor in neuroblastoma. The senescence signature was also meaningful at the single-cell level and the nomogram was shown to have high accuracy and high clinical benefit.</p><p><strong>Conclusions: </strong>We comprehensively evaluated the significance of cellular senescence in neuroblastoma and concluded that it was significantly associated with immune characteristics and overall prognosis. Based on the expression levels of CSAGs, we developed the CSRS, which was a reliable tool to contribute to prognostic assessment and clinical decision making.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"469-486"},"PeriodicalIF":1.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028558","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}