Functional & Integrative Genomics最新文献

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Single-cell RNA sequencing revealed changes in the tumor microenvironment induced by radiotherapy for cervical cancer and the molecular mechanism of mast cells in immunosuppression
IF 3.9 4区 生物学
Functional & Integrative Genomics Pub Date : 2025-03-14 DOI: 10.1007/s10142-025-01564-7
Lujiadai Xue, Linzhi Gao, Shimin Zhou, Chaofan Yan, Xian Zhang, Wei Lin, Hu Li, Yuan Shen, Xiaoyu Wang
{"title":"Single-cell RNA sequencing revealed changes in the tumor microenvironment induced by radiotherapy for cervical cancer and the molecular mechanism of mast cells in immunosuppression","authors":"Lujiadai Xue,&nbsp;Linzhi Gao,&nbsp;Shimin Zhou,&nbsp;Chaofan Yan,&nbsp;Xian Zhang,&nbsp;Wei Lin,&nbsp;Hu Li,&nbsp;Yuan Shen,&nbsp;Xiaoyu Wang","doi":"10.1007/s10142-025-01564-7","DOIUrl":"10.1007/s10142-025-01564-7","url":null,"abstract":"<div><p>Radiotherapy (RT) is an important treatment for cervical cancer (CC), effectively controlling tumor growth and improving survival rates. However, radiotherapy-induced cell heterogeneity and its underlying mechanisms remain unclear, which may potentially impact treatment efficacy. This study aims to investigate tumor microenvironment changes following radiotherapy for CC, hoping to provide evidence to improve the therapeutic effects of radiotherapy. For the first time, we applied single-cell RNA sequencing (scRNA-seq) to analyze tissue samples from three CC patients pre- and post-radiotherapy. We obtained gene expression data from 52,506 cells to identify the cellular changes and molecular mechanisms induced by radiotherapy. Radiotherapy significantly alters cellular composition and gene expression within the tumor microenvironment (TME), notably upregulating mast cell expression. Mast cells are involved in multiple cell axes in the CC ecosystem after radiotherapy, and play a pivotal role in tumor immunosuppression and matrix remodeling. scRNA-seq revealed gene expression variations among cell types after radiotherapy, underscoring the importance of specific cell types in modulating the TME post-treatment. This study revealed the molecular mechanism of radiotherapy for CC and the role of mast cells, providing a foundation for optimizing the personalized treatment of CC.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612259","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}
引用次数: 0
Combined transcriptomic and proteomic analyses reveal relevant myelin features in mice with ischemic stroke
IF 3.9 4区 生物学
Functional & Integrative Genomics Pub Date : 2025-03-14 DOI: 10.1007/s10142-025-01573-6
Qiuyang Qian, Hao Lyu, Wei Wang, Qiwen Wang, Desheng Li, Xiaojia Liu, Yi He, Mei Shen
{"title":"Combined transcriptomic and proteomic analyses reveal relevant myelin features in mice with ischemic stroke","authors":"Qiuyang Qian,&nbsp;Hao Lyu,&nbsp;Wei Wang,&nbsp;Qiwen Wang,&nbsp;Desheng Li,&nbsp;Xiaojia Liu,&nbsp;Yi He,&nbsp;Mei Shen","doi":"10.1007/s10142-025-01573-6","DOIUrl":"10.1007/s10142-025-01573-6","url":null,"abstract":"<div><p>Ischemic stroke (IS), a leading cause of global disability and mortality, is characterized by white matter damage and demyelination. Despite advances, the molecular mechanisms driving post-IS myelin pathology remain poorly understood, limiting therapeutic development. This study investigates key myelin-related genes (MRGs) and their regulatory networks to identify novel therapeutic targets. A transient middle cerebral artery occlusion (MCAO) model was established in C57BL/6 mice, with brain tissues collected at four timepoints (Sham0D, MCAO0D, MCAO7D, MCAO14D). Transcriptomic and proteomic sequencing were performed, followed by soft clustering (Mfuzz), functional enrichment (GO/KEGG), and ROC analysis to identify key MRGs. Competing endogenous RNA (ceRNA) networks were constructed, and drug prediction was conducted using the Comparative Toxicogenomics Database (CTD) and molecular docking. Expression validation was performed via qRT-PCR and Western blot. Integrated multi-omics analysis identified <i>Wasf3</i> and <i>Slc25a5</i> as key MRGs, enriched in mitochondrial respiration, calcium metabolism, and cytoskeletal regulation. The AUC values of the one-to-one model scores were all greater than 0.7, suggesting that <i>Wasf3</i> and <i>Slc25a5</i> were able to effectively discriminate between samples from different time points. A ceRNA network revealed critical interactions, including the <i>Wasf3-mmu-miR-423-5p-H19</i> axis, linking apoptosis and myelin dysfunction. Drug prediction highlighted valproic acid (VPA) as a high-affinity binder for both genes (binding energies: − 4.2 and − 4.7 kcal/mol), suggesting its potential as a therapeutic candidate for IS. Experimental validation confirmed significant downregulation of <i>Wasf3</i> mRNA (<i>p</i> &lt; 0.01) and protein (<i>p</i> = 0.069) post-IS, while <i>Slc25a5</i> showed no significant changes, potentially due to sample size limitations. This study establishes <i>Wasf3</i> and <i>Slc25a5</i> as pivotal regulators of post-IS myelin pathology and proposes VPA as a promising therapeutic candidate to enhance remyelination. The findings underscore the utility of multi-omics approaches in bridging molecular mechanisms to clinical translation, offering new strategies for IS diagnosis and treatment.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-025-01573-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612258","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}
引用次数: 0
Predictive and personalized approaches for idiopathic pulmonary fibrosis: a Wnt-related gene set scoring framework integrating single-cell sequencing, spatial transcriptomics, and machine learning for diagnosis and prognosis
IF 3.9 4区 生物学
Functional & Integrative Genomics Pub Date : 2025-03-13 DOI: 10.1007/s10142-025-01571-8
Qijian Ji, Lei Jiang, Fei Gao, Jiwei Hou
{"title":"Predictive and personalized approaches for idiopathic pulmonary fibrosis: a Wnt-related gene set scoring framework integrating single-cell sequencing, spatial transcriptomics, and machine learning for diagnosis and prognosis","authors":"Qijian Ji,&nbsp;Lei Jiang,&nbsp;Fei Gao,&nbsp;Jiwei Hou","doi":"10.1007/s10142-025-01571-8","DOIUrl":"10.1007/s10142-025-01571-8","url":null,"abstract":"","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602222","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}
引用次数: 0
Differential miRNA expression and regulatory mechanisms in pigmentation and fiber development of white and brown cotton (Gossypium hirsutum)
IF 3.9 4区 生物学
Functional & Integrative Genomics Pub Date : 2025-03-12 DOI: 10.1007/s10142-025-01568-3
Sagar Prasad Nayak, Priti Prasad, Shafquat Fakhrah, Debashree Pattanaik, Sumit Kumar Bag, Chandra Sekhar Mohanty
{"title":"Differential miRNA expression and regulatory mechanisms in pigmentation and fiber development of white and brown cotton (Gossypium hirsutum)","authors":"Sagar Prasad Nayak,&nbsp;Priti Prasad,&nbsp;Shafquat Fakhrah,&nbsp;Debashree Pattanaik,&nbsp;Sumit Kumar Bag,&nbsp;Chandra Sekhar Mohanty","doi":"10.1007/s10142-025-01568-3","DOIUrl":"10.1007/s10142-025-01568-3","url":null,"abstract":"<div><p>Cotton (<i>Gossypium hirsutum</i>) is a major global natural fiber crop used in the textile industry. Although white colored cotton remains the most popular form of cultivated cotton, colored varieties could replace chemically dyed fibers and provide more environmental friendly alternatives. In order to investigate the role of miRNAs in fiber color, we selected white and brown cotton varieties for comparative investigations. Through small RNA sequencing, a number of known miRNA families were discovered (74 in white cotton and 61 in brown cotton, with 44 shared) in which 11 miRNA families were significantly elevated in brown cotton variety. Functional enrichment and network analysis of target genes of these miRNAs revealed their regulatory role in secondary metabolite biosynthesis pathway, particularly the flavonoids pathway, which are known to be associated with fiber coloration. Pigmentation and developmental-related miRNA members such as miR396e-5p, miR167l, and miR1446 were also significantly enriched. Real-time PCR results suggest the regulatory role of miRNAs in these two cotton varieties. Furthermore, 30 and 25 novel miRNAs were also identified in white and brown cotton, respectively. Our findings also show miRNAs associated with fiber coloration and development through the intricate networks of miRNA and targets. Understanding these systems may provide novel insights on improving the fiber color and quality.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602255","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}
引用次数: 0
Integrative single-cell and bulk RNA-seq analysis identifies lactylation-related signature in osteosarcoma
IF 3.9 4区 生物学
Functional & Integrative Genomics Pub Date : 2025-03-12 DOI: 10.1007/s10142-025-01559-4
Zhou Xie, Xiao Qu, Jun Zhang, Yanran Huang, Zhao Runhan, Dagang Tang, Ningdao Li, Zhule Wang, Xiaoji Luo
{"title":"Integrative single-cell and bulk RNA-seq analysis identifies lactylation-related signature in osteosarcoma","authors":"Zhou Xie,&nbsp;Xiao Qu,&nbsp;Jun Zhang,&nbsp;Yanran Huang,&nbsp;Zhao Runhan,&nbsp;Dagang Tang,&nbsp;Ningdao Li,&nbsp;Zhule Wang,&nbsp;Xiaoji Luo","doi":"10.1007/s10142-025-01559-4","DOIUrl":"10.1007/s10142-025-01559-4","url":null,"abstract":"<div><p>Osteosarcoma is the most common bone tumor and a highly aggressive malignant neoplasm. This study aims to elucidate the role of lactylation-related genes (LRGs) in osteosarcoma, with the goal of improving prognostic accuracy and enhancing the efficacy of immunotherapy. Using public datasets, we integrated differential and correlated genes based on single-cell sequencing AUCell scores and performed enrichment analysis and risk model construction on these genes. A total of 277 genes were found to be intricately linked with lactate metabolism. Using the uni-Cox and LASSO algorithm, nine key genes were identified, demonstrating strong predictive power for the prognosis of Osteosarcoma patients. Notably, changes were observed at the levels of immune checkpoints, the tumor microenvironment (TME), drug sensitivity, and immune cell infiltration. This study paves the way for targeted drug interventions, thereby opening avenues for improving clinical outcomes in osteosarcoma.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594829","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}
引用次数: 0
MAZ-mediated LAMA5 transcription activation promotes gastric cancer progression through the STAT3 signaling
IF 3.9 4区 生物学
Functional & Integrative Genomics Pub Date : 2025-03-12 DOI: 10.1007/s10142-025-01574-5
Yu Wang, Jiazhong Xu, Hongxia Zhang, Xiaobo Guo, Hongjun Liu, Qinhui Sun
{"title":"MAZ-mediated LAMA5 transcription activation promotes gastric cancer progression through the STAT3 signaling","authors":"Yu Wang,&nbsp;Jiazhong Xu,&nbsp;Hongxia Zhang,&nbsp;Xiaobo Guo,&nbsp;Hongjun Liu,&nbsp;Qinhui Sun","doi":"10.1007/s10142-025-01574-5","DOIUrl":"10.1007/s10142-025-01574-5","url":null,"abstract":"<div><p>Laminin subunit alpha-5 (LAMA5) has been identified as an oncogene in many cancers, while its role and mechanism in gastric cancer (GC) remain to be explored. Here, the influences of LAMA5 knockdown on GC were investigated in vitro and in vivo. LAMA5 expression was silenced in GC cells alone or in combination with the signal transducer and activator of transcription 3 (STAT3) activator Colivelin, followed by CCK-8, colony formation, EdU, flow cytometry, wound healing assay, and Transwell assay. The regulatory relationship between Myc-associated zinc finger protein (MAZ) and LAMA5 was characterized by ChIP and luciferase reporter analysis. The effect of knockdown of MAZ alone or in combination with LAMA5 overexpression on GC was investigated in vitro and in vivo. LAMA5 was highly expressed in GC cells, and knockdown of LAMA5 inhibited GC cell malignant aggressiveness, which was reversed by the Colivelin treatment. The transcription factor MAZ bound to the promoter of LAMA5 to activate its transcription, and the anti-tumor effects of sh-MAZ on GC cells in vitro and in vivo were overturned by LAMA5 overexpression. In conclusion, MAZ promotes GC cell proliferation and migration by the LAMA5/STAT3 axis, implying that this axis can function as a target for GC therapy.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-025-01574-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594830","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}
引用次数: 0
Regulatory dynamics of Nanog in chondrocyte dedifferentiation: role of KLF4/p53 and p38/AKT signaling
IF 3.9 4区 生物学
Functional & Integrative Genomics Pub Date : 2025-03-11 DOI: 10.1007/s10142-025-01572-7
Young Seok Eom, Song Ja Kim
{"title":"Regulatory dynamics of Nanog in chondrocyte dedifferentiation: role of KLF4/p53 and p38/AKT signaling","authors":"Young Seok Eom,&nbsp;Song Ja Kim","doi":"10.1007/s10142-025-01572-7","DOIUrl":"10.1007/s10142-025-01572-7","url":null,"abstract":"<div><p>Homeobox protein Nanog, a member of the transcription factor family, plays a crucial role in maintaining the pluripotency and self-renewal of embryonic stem cells. Due to its diverse activities, Nanog has been identified in multiple cell types, including embryonic stem cells (ESCs) and cancer stem cells (CSCs). However, its molecular mechanism in chondrocytes remains unclear. In this study, we explored the effects of Nanog on chondrocytes and its interaction with chondrocyte-specific proteins. Chondrocytes were transfected with a Nanog cDNA vector, resulting in reduced expression of the chondrogenic markers Type II collagen and SOX9, as confirmed by western blot, RT-PCR, and immunofluorescence. Following siRNA transfection, the dedifferentiation effect of Nanog was reversed, restoring Type II collagen and SOX9 expression. We also discovered that the mechanism by which Nanog affects chondrocytes is closely linked to p53 and KLF4. Overexpression of KLF4 induced the phosphorylation of p53, and phospho-p53 directly inhibited Nanog expression. Moreover, the p53 activator Nutlin-3 A accelerated Nanog degradation, while the p53 inhibitor Pifithrin-α stabilized Nanog. Stabilized Nanog continued to promote chondrocyte dedifferentiation. Additional experiments were performed to identify the signaling pathways involved in Nanog-induced chondrocyte dedifferentiation. Our results showed that Nanog overexpression in chondrocytes significantly impacted the p38 kinase and AKT signaling pathways. Inhibition of p38 and AKT with SB203580 and LY294002 reduced Nanog expression and partially restored Type II collagen levels. Conversely, activation with anisomycin(ANS) and 740 Y-P enhanced Nanog expression, further reducing Type II collagen levels. To investigate Nanog’s role in early development in vivo, we injected Nanog expression vectors into zebrafish embryos. The injected zebrafish exhibited structural defects in craniofacial cartilage, confirming Nanog’s involvement in chondrocyte differentiation. These findings suggest that Nanog induces chondrocyte dedifferentiation, and this process can be modulated via the p53/KLF4 and p38/AKT pathways.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583426","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}
引用次数: 0
Genome-wide identification of F-box-LRR gene family and the functional analysis of CsFBXL13 transcription factor in tea plants
IF 3.9 4区 生物学
Functional & Integrative Genomics Pub Date : 2025-03-10 DOI: 10.1007/s10142-025-01569-2
Xiangya Dou, Siyi Xie, Jinbo Wang, Xiaohua Shen, Shuoqian Liu, Na Tian
{"title":"Genome-wide identification of F-box-LRR gene family and the functional analysis of CsFBXL13 transcription factor in tea plants","authors":"Xiangya Dou,&nbsp;Siyi Xie,&nbsp;Jinbo Wang,&nbsp;Xiaohua Shen,&nbsp;Shuoqian Liu,&nbsp;Na Tian","doi":"10.1007/s10142-025-01569-2","DOIUrl":"10.1007/s10142-025-01569-2","url":null,"abstract":"<div><p>This study focused on the identification and functional analysis of the F-box-LRR (FBXL) protein family in tea tree (<i>Camellia sinensis</i>), aiming to reveal its role in spring bud germination and environmental adaptation. Thirty-seven members of the tea tree F-box-LRR gene family were identified and systematically analyzed for their chromosomal localization, gene structure, conserved motifs, and cis-acting elements by bioinformatics methods. It was found that these genes were distributed on 14 chromosomes, with strong conserved and inter-gene covariance characteristics. Cis-acting element analysis showed that the F-box-LRR family members were associated with signals such as low temperature, gibberellin and growth hormone, which may play a key role in spring low-temperature germination. In addition, the study verified that the CsWRKY40 transcription factor directly binds to the promoter region of the <i>CsFBXL13</i> gene and significantly activates its expression by subcellular localization, yeast one-hybridization and dual luciferase assays, revealing the important function of the CsWRKY40-<i>CsFBXL13</i> regulatory axis in low-temperature response and spring bud germination in tea tree. This study not only expands the understanding of the F-box-LRR protein family, but also provides potential molecular targets for improving the resistance and productivity of tea tree through molecular breeding.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-025-01569-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581227","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}
引用次数: 0
Transcriptomic profiling reveals mechanism, therapeutic potential, and prognostic value of cancer stemness characteristic in nasopharyngeal carcinoma
IF 3.9 4区 生物学
Functional & Integrative Genomics Pub Date : 2025-03-07 DOI: 10.1007/s10142-025-01561-w
Jin-Wei Chen, Run-Nan Shen, Jiang-Quan Zhu, Ying-Hang Wang, Liang-Min Fu, Yu-Hang Chen, Jia-Zheng Cao, Jin-Huan Wei, Jun-Hang Luo, Jia-Ying Li, Cheng-Peng Gui
{"title":"Transcriptomic profiling reveals mechanism, therapeutic potential, and prognostic value of cancer stemness characteristic in nasopharyngeal carcinoma","authors":"Jin-Wei Chen,&nbsp;Run-Nan Shen,&nbsp;Jiang-Quan Zhu,&nbsp;Ying-Hang Wang,&nbsp;Liang-Min Fu,&nbsp;Yu-Hang Chen,&nbsp;Jia-Zheng Cao,&nbsp;Jin-Huan Wei,&nbsp;Jun-Hang Luo,&nbsp;Jia-Ying Li,&nbsp;Cheng-Peng Gui","doi":"10.1007/s10142-025-01561-w","DOIUrl":"10.1007/s10142-025-01561-w","url":null,"abstract":"<div><p>Nasopharyngeal carcinoma (NPC) recurrence, distant metastasis, and drug resistance remain significant obstacles in clinical prognosis. Cancer stemness is hypothesized to be a key contributor, though direct evidence is sparse. We utilized bioinformatics and machine learning techniques on single-cell RNA-seq and bulk transcriptomic datasets, complemented by basic experiments, to investigate stemness-based characteristics in NPC. Our analysis identified two potential developmental trajectories of nasopharyngeal cancer cells, each exhibiting varying levels of stemness. We subsequently identified and validated a cancer stemness-related signature (STEM-signature). Single-cell profiling revealed enrichment of LAYN + CD8 + , CTLA4 + CD4 + , CXCL13 + CD4 + T cells, tumor-associated macrophages, and CD14 + monocytes in NPC patients with high stemness. NicheNet analysis suggested these immune cells regulate cancer stemness. Bulk transcriptomic analysis corroborated these findings, indicating a poor therapeutic response in high-stemness NPC. We predicted 13 potential drugs and identified 13 stemness-related miRNAs for NPC with high stemness. A Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model, based on this miRNA signature, predicted overall survival with an AUC of 0.71 and 0.72 in validation and testing sets, respectively. The miRNA-based stemness signature outperformed previous established signatures. Multivariate Cox regression analysis indicated that our prognostic signature could serve as an independent prognostic factor (p &lt; 0.001). Basic experiments showed that miR-300, miR-361-5p, miR-1246, and miR-1290 enhanced the stemness characteristics of NPC cells, promoting proliferation, invasion, and migration. These findings suggest that these four stemness-related miRNAs could serve as therapeutic targets, potentially improving therapeutic responses by targeting stemness-related genes.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571144","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}
引用次数: 0
Transcriptome analysis of the hypothalamus and testes in Brandt’s Vole: new insights into mechanisms of photoperiodic plasticity in postnatal testicular development
IF 3.9 4区 生物学
Functional & Integrative Genomics Pub Date : 2025-03-07 DOI: 10.1007/s10142-025-01562-9
Lewen Wang, Yaqi Ying, Ning Li, Ying Song, Lijuan Zhao, Hong Sun, Zhenlong Wang, Xiao-Hui Liu, Dawei Wang
{"title":"Transcriptome analysis of the hypothalamus and testes in Brandt’s Vole: new insights into mechanisms of photoperiodic plasticity in postnatal testicular development","authors":"Lewen Wang,&nbsp;Yaqi Ying,&nbsp;Ning Li,&nbsp;Ying Song,&nbsp;Lijuan Zhao,&nbsp;Hong Sun,&nbsp;Zhenlong Wang,&nbsp;Xiao-Hui Liu,&nbsp;Dawei Wang","doi":"10.1007/s10142-025-01562-9","DOIUrl":"10.1007/s10142-025-01562-9","url":null,"abstract":"<div><p>Postnatal gonadal development is regulated by photoperiod via the hypothalamus, especially in seasonal breeding small rodents. However, the precise molecular mechanisms remain unclear. In this study, we conducted a comparative analysis of the transcriptomes of the hypothalamus and testes in 10-week-old male Brandt’s voles born under long (LP, 16L:8D) and short photoperiod (SP, 8L:16D) conditions. Results indicate that the SP group exhibited significantly smaller testes with spermatogenesis halted before meiosis, identifying 129 differentially expressed genes (DEGs) in the hypothalamus and 21,673 DEGs in the testes. In the hypothalamus, genes involved in the thyroid hormone and retinoic acid (RA) pathway were notably altered under SP conditions, including decreased <i>Tshb</i> and <i>Cga</i> expression, increased <i>Dio3</i>, and reduced <i>Crabp1</i> and <i>Lrat</i>, highlighting their key roles in SP signaling. In the testes, downregulated genes were significantly enriched in male reproduction-related GO terms and metabolic KEGG pathways, such as steroid hormone biosynthesis and retinol metabolism. Key genes for testosterone synthesis (e.g. <i>Star</i>, <i>Cyp11a1</i>) and RA synthesis (e.g. <i>Rdh10</i>, <i>Rdh11</i>) were downregulated, while those linked to RA degradation (<i>Cyp26b1</i>) and undifferentiated spermatogonia maintenance (e.g. <i>Gdnf</i>, <i>Gfra1</i>) were upregulated. These findings outline a molecular microenvironment that favors the preservation of undifferentiated spermatogonia over their differentiation from the hypothalamus to the testes. This study firstly provides valuable insights into the transcriptomic basis of SP-inhibited testicular development in Brandt’s voles.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143564457","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}
引用次数: 0
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