Genes & genomics最新文献

{"title":"CTHRC1 expresses in cancer-associated fibroblasts and is associated with resistance to anti-androgen therapy in prostate cancer.","authors":"Hai-Qi Liang, Qi-Huan He, Qiu-Ju Wei, Qi-Zhou Mo, Guang-Lin Yang, Fa-Ye Wei, Li-Wei Wei, Yu-Jian Li, Min Qin, Ji-Wen Cheng","doi":"10.1007/s13258-025-01624-z","DOIUrl":"10.1007/s13258-025-01624-z","url":null,"abstract":"<p><strong>Background: </strong>CTHRC1 overexpresses in prostate cancer and is associated with the proliferation, invasion and migration of prostate cancer cells. However, the roles and mechanisms of CTHRC1 expression in prostate cancer prognosis and treatment outcomes remain unknown.</p><p><strong>Objective: </strong>This study aimed to explore the expression and gene function of CTHRC1 in prostate cancer, investigate the prognostic value and potential effect in the treatment of prostate cancer.</p><p><strong>Methods: </strong>Bulk and single-cell RNA sequencing analyses were used to evaluate the expression of CTHRC1 in prostate cancer. All data used in the study were obtained from publicly available sources to ensure transparency. Study enrolled 1999 cases of prostate cancer and 531 normal controls. Single-cell RNA sequencing profile included 62,995 cells from seven prostate primary tumors. CTHRC1 expression and prognosis analyses were conducted with these samples and verified by immunohistochemical staining. CIBERSORT algorithm was used to assess the tumor immune infiltrating cells based on bulk mRNA sequencing profiles. Genomics of drug sensitivity in cancer (GDSC) database was used to predict IC50 to anti-androgen therapy (ADT) drugs of the samples.</p><p><strong>Results: </strong>CTHRC1 expressed in prostate cancer was higher than that in normal prostate tissue, and the expression increased with the progress of prostate cancer. CTHRC1 was the risk factor of progression-free interval (PFI). CTHRC1 was positively correlated with the infiltration of tumor-associated macrophages (TAMs). Myofibroblast-like cancer-associated fibroblasts (myCAFs) were the major CTHRC1 expressers in prostate cancer. TGF-β signaling activated in CTHRC1-positive myCAFs and was involved in TAMs polarization. Biological functions of myCAFs were enriched in hormone response and metabolism. CTHRC1 may regulate androgen receptor signaling through CCN2/CAV1/AR pathway. Moreover, ADT drug Bicalutamide and AZD3514 were less sensitive in the high CTHRC1 expression tumors.</p><p><strong>Conclusions: </strong>As a potential molecular target of ADT resistance in prostate cancer, CTHRC1 provides a new promising molecular approach for the diagnosis and treatment of prostate cancer.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"541-557"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500585","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":"Analysing glycolysis-related genes reveals the prognostic and diagnostic relevance of IER3 and AGRN in colorectal cancer.","authors":"Samaneh Dalali, Fatemeh Kaviani, Mohammad Mahdevar, Andisheh Oroujalian, Maryam Peymani","doi":"10.1007/s13258-025-01618-x","DOIUrl":"10.1007/s13258-025-01618-x","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a significant global health issue, with early detection being critical to improving patient survival. Dysregulation of the glycolysis pathway plays a pivotal role in CRC progression, but specific gene-level mechanisms remain underexplored.</p><p><strong>Objective: </strong>This study aimed to investigate the role of glycolysis-related genes in CRC development and identify potential diagnostic and prognostic biomarkers.</p><p><strong>Methods: </strong>We utilized The Cancer Genome Atlas (TCGA) dataset to perform differential expression analysis of glycolysis-related genes in CRC. Protein-protein interaction (PPI) network analysis was conducted to identify central hub genes. The diagnostic potential of selected genes was evaluated using ROC curve analysis, while their expression levels were validated through RT-qPCR.</p><p><strong>Results: </strong>IER3 and AGRN were identified as significantly upregulated genes associated with reduced survival rates in CRC patients. PPI analysis revealed their roles as central hub genes within the glycolysis pathway. ROC curve analysis demonstrated their ability to distinguish CRC patients from healthy individuals. Validation through RT-qPCR confirmed their significant overexpression in CRC samples, highlighting their involvement in disease progression.</p><p><strong>Conclusion: </strong>IER3 and AGRN are critical components of the glycolysis pathway, driving CRC development and progression while also showing potential as biomarkers for predicting outcomes, diagnosing CRC, and serving as treatment targets.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"509-520"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566913","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":"Ectopic expression of AtMYB115 and AtMYB118 induces green tissue formation in non-green organs of Arabidopsis thaliana.","authors":"Hyeon-Ung Jang, Sang-Kee Song","doi":"10.1007/s13258-025-01639-6","DOIUrl":"10.1007/s13258-025-01639-6","url":null,"abstract":"<p><strong>Background: </strong>A dominant mutant, green root-dominant (grt-D), which exhibits a green-root phenotype, was identified using the GAL4-UAS activation tagging system in the Q2610 enhancer trap line of Arabidopsis thaliana (Arabidopsis).</p><p><strong>Objective: </strong>To identify the gene responsible for the grt-D phenotype and investigate whether its ectopic expression induces green petal formation.</p><p><strong>Methods: </strong>The gene responsible for the grt-D phenotype was identified via thermal asymmetric interlaced-polymerase chain reaction (PCR). The cloned gene and its homolog were expressed under the control of the Q2610 enhancer for root tip expression and the APETALA3 (AP3) or PISTILLATA (PI) promoter for petal-preferential expression.</p><p><strong>Results: </strong>The 5 × UAS tag in grt-D was located 111 base pairs upstream of the start codon of AtMYB115. Ectopic expression of AtMYB115 or its closest homolog, AtMYB118, under the Q2610 enhancer recapitulated the grt-D green-root phenotype, indicating functional equivalence between the two genes. To examine their effect on petal development, AtMYB115 and AtMYB118 were expressed under the AP3 and PI promoters. The resulting transgenic lines (AP3 >  > AtMYB115, AP3 >  > AtMYB118, PI >  > AtMYB115, and PI >  > AtMYB118) developed short, pale green petals and sterile stamens. The green petals exhibited reduced expression of STAY-GREEN 1, which encodes Mg-dechelatase, a key enzyme involved in chlorophyll degradation, suggesting that the green-petal phenotype results from impaired chlorophyll breakdown.</p><p><strong>Conclusion: </strong>These findings demonstrate that the ectopic expression of AtMYB115 and AtMYB118 induces green tissue development in non-green organs of Arabidopsis.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"587-597"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729574","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":"RepID depletion enhances TWS119-induced erythropoiesis through chromatin reprogramming and transcription factor recruitment.","authors":"Seon-Mi Ok, Jae-Hyun Jo, Hyo Je Cho, Sang-Min Jang","doi":"10.1007/s13258-025-01627-w","DOIUrl":"10.1007/s13258-025-01627-w","url":null,"abstract":"<p><strong>Background: </strong>Erythrocytes, derived from hematopoietic stem cells, are essential for oxygen transport, ensuring survival in all vertebrate animals. The process of erythropoiesis is associated with gene expression changes, but many key regulatory factors that govern erythroid differentiation remain to be fully understood.</p><p><strong>Objective: </strong>This study investigates the role of TWS119, a known GSK3β inhibitor, in inducing erythropoiesis in K562 erythroleukemia cells and explores the impact of Replication initiation determinant protein (RepID) depletion on the process.</p><p><strong>Methods: </strong>K562 cells were treated with TWS119 and erythropoiesis markers including various erythrocytic phenotypes were assessed. Chromatin-immunoprecipitation analysis was employed to examine the changes in chromatin structure and gene expression regulation. The impact of RepID depletion on TWS119-induced erythropoiesis was also evaluated by analyzing globin promoter euchromatinization and NRF2 binding.</p><p><strong>Results: </strong>TWS119 treatment led to erythrocytic phenotypes in K562 cells, such as red pellet formation, enucleation, and nucleus condensation, along with the upregulation of erythropoiesis markers. Furthermore, RepID depletion accelerated TWS119-mediated erythropoiesis. Chromatin-immunoprecipitation analysis revealed euchromatinization of the globin promoter and enhanced NRF2 binding in RepID-depleted cells, suggesting a mechanism of gene expression regulation during erythropoiesis.</p><p><strong>Conclusion: </strong>This study demonstrates that TWS119 can induce erythropoiesis in K562 cells, and that RepID depletion enhances this process by modulating chromatin structure and facilitating transcription factor binding. These findings highlight a RepID-dependent mechanism in the regulation of gene expression during erythropoiesis.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"533-540"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656906","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":"Prognostic and immunological role of LASP2 in clear cell renal cell carcinoma.","authors":"Libo Chen, Nanhui Chen, Zhouzhou Xie, Yuchen Xiao, Huiming Jiang","doi":"10.1007/s13258-024-01612-9","DOIUrl":"10.1007/s13258-024-01612-9","url":null,"abstract":"<p><strong>Background: </strong>Clear cell renal cell carcinoma (ccRCC) represents a common renal carcinoma subtype influenced by the immune microenvironment. LIM and SH3 Protein 2 (LASP2), an actin-binding protein within the nebulin family, contributes to cellular immunity and adhesion mechanisms.</p><p><strong>Objective: </strong>This study aimed to clarify the immunological and prognostic relevance of LASP2 in ccRCC.</p><p><strong>Methods: </strong>Using clinical and expression data from TCGA, LASP2 expression levels were analyzed alongside clinicopathological features in ccRCC patients. Validation was conducted through real-world samples and tissue microarrays. Comprehensive analysis using online databases examined genetic mutations, DNA methylation patterns, and immune microenvironment characteristics. Gene set enrichment analysis (GSEA) provided insights into LASP2's potential mechanisms in ccRCC.</p><p><strong>Results: </strong>LASP2 expression was notably reduced and correlated with adverse clinicopathological features and prognosis in ccRCC patients. Prognostic associations were identified across multiple CpG DNA methylation sites. LASP2 levels showed significant correlations with immune cell infiltration and checkpoint genes, including PDCD1 and CTLA4. GSEA findings highlighted LASP2's enrichment within metabolic pathways and signaling networks, such as fatty acid metabolism, TGF-β signaling, and epithelial-mesenchymal transition.</p><p><strong>Conclusion: </strong>LASP2 emerged as an immune-associated biomarker linked to poorer survival outcomes in ccRCC, suggesting its potential as a novel anti-cancer target and prognostic indicator in ccRCC.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"625-636"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876918","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":"Alternative splicing of CHI3L1 regulates protein secretion through conformational changes.","authors":"Haesoo Jung, Yong-Eun Kim, Eun-Mi Kim, Kee K Kim","doi":"10.1007/s13258-025-01635-w","DOIUrl":"10.1007/s13258-025-01635-w","url":null,"abstract":"<p><strong>Background: </strong>Alternative splicing (AS) plays a crucial role in regulating protein function through the generation of structurally distinct isoforms.</p><p><strong>Objective: </strong>We identify a novel splicing event in Chitinase 3-like 1 (CHI3L1) that modulates its secretion through conformational changes.</p><p><strong>Methods: </strong>CHI3L1 alternative splicing was analyzed using the GTEx dataset. The regulation of CHI3L1 splicing was examined in response to THP-1 and BEAS-2B cells using RT-PCR. Structural modeling of CHI3L1 isoforms was conducted with AlphaFold to predict conformational changes caused by exon 8 exclusion. Protein expression and secretion levels of CHI3L1 isoforms were analyzed by Western blotting.</p><p><strong>Results: </strong>Analysis of the GTEx dataset revealed tissue-specific regulation of CHI3L1 exon 8, with pronounced exclusion in lung tissue. The splicing pattern of CHI3L1 was dynamically regulated during THP-1 macrophage differentiation and by cell density in lung-derived epithelial BEAS-2B cells, suggesting its responsiveness to cellular context. While both full-length and exon 8-excluded CHI3L1 proteins showed cytoplasmic localization, structural analysis using AlphaFold revealed that exon 8 exclusion significantly altered the orientation of the signal peptide. Consequently, exon 8-excluded CHI3L1 exhibited minimal secretion into the culture medium compared to the full-length protein.</p><p><strong>Conclusion: </strong>These findings demonstrate that alternative splicing-mediated exclusion of exon 8 serves as a novel regulatory mechanism controlling CHI3L1 secretion through conformational changes, providing new insights into the post-transcriptional regulation of secreted proteins.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"571-579"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700370","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":"Whole transcriptome profiling of cardiac injury: insights from a neonatal mouse sepsis model.","authors":"Wenjin Feng, Huanqi Tang, Chengshuai Li, Xiaohui Kong, Xueyun Ren, Huabin Wang","doi":"10.1007/s13258-025-01632-z","DOIUrl":"10.1007/s13258-025-01632-z","url":null,"abstract":"<p><strong>Background: </strong>Neonatal sepsis is characterized by an excessive immune response, often leading to multiple organ failure, including cardiac injury, and is a major cause of morbidity and mortality in newborns. Understanding the molecular mechanisms of sepsis-induced cardiac injury is crucial for developing therapeutic strategies.</p><p><strong>Objective: </strong>To investigate transcriptomic changes and identify potential altered genes associated with cardiac injury in a neonatal sepsis model.</p><p><strong>Methods: </strong>A neonatal sepsis model was established by cecal slurry injection. RNA sequencing analysis was performed on cardiac tissues from sepsis and control groups, followed by functional enrichment analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Interaction networks among mRNA, lncRNA, circRNA, and miRNA were constructed, and key regulatory genes were identified through protein-protein interaction (PPI) analysis.</p><p><strong>Results: </strong>A total of 1537 differentially expressed mRNAs, 287 lncRNAs, and 730 circRNAs were identified. Functional analysis revealed significant involvement in immune response and inflammatory regulation. PPI network analysis identified six key genes-Ccl5, Il-6, Pole, Mcm2, Mcm5, Mcm10-that were significantly expressed in sepsis-induced cardiac tissue. Additionally, lncRNAs and circRNAs were found to participate in myocardial injury by regulating immune and inflammatory pathways.</p><p><strong>Conclusions: </strong>This study identified six key genes involved in immune and inflammatory responses, playing critical roles in sepsis-induced cardiac injury in neonates. These findings provide new insights into the pathogenesis of sepsis-induced cardiac injury and offer potential therapeutic targets.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"599-613"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669634","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":"Report of two coinfections of human adenovirus and sapovirus in patients with acute gastroenteritis from China.","authors":"Xin Wang, Yaqing He, Mingda Hu, Wanqiu Liu, Kexin Li, Qiao Li, Shaofu Qiu, Lianqun Jin, Hailong Zhang, Boqian Wang, Chuanfu Zhang, Zhixi Peng, Long Chen, Xiaofeng Hu, Hongguang Ren, Hongbin Song","doi":"10.1007/s13258-025-01637-8","DOIUrl":"10.1007/s13258-025-01637-8","url":null,"abstract":"<p><strong>Background: </strong>Coinfections involving multiple diarrheal viruses have gained increasing recognition as a significant cause of acute gastroenteritis in recent years. Understanding the genetic diversity and evolutionary relationships of these viruses is crucial for effective outbreak identification and tracking.</p><p><strong>Objective: </strong>To report two cases of HAdV and SaV coinfections and elucidate the genetic diversity and evolutionary patterns of these viruses through whole-genome sequencing (WGS) and phylogenetic analysis.</p><p><strong>Methods: </strong>A total of 873 diarrheal stool samples were collected from sentinel hospitals in Shenzhen, China, in 2021. The collected stool samples were identified using RT-PCR and positive samples were subjected to WGS on the NovaSeq platform. phylogenetic trees were constructed using MEGA to analyze genetic relationships.</p><p><strong>Results: </strong>The sequencing results showed that both samples were human adenovirus type 41, which clustered in two distinct evolutionary clades. Additionally, we also retrieved the complete genome of sapovirus (GI.1 genotype) from the same sample. Phylogenetic analysis revealed that they were similar to previously reported strains, belonging to the clade predominating in China.</p><p><strong>Conclusions: </strong>This study reveals the genetic diversity of epidemic strains involved in coinfections of human adenovirus and sapovirus. The findings establish a groundwork for the identification and traces of acute gastroenteritis outbreaks.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"581-586"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735758","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":"Backtracking identification techniques for predicting unclear bacterial taxonomy at species level: molecular diagnosis-based bacterial classification.","authors":"Yeseul Choi, Jinuk Jeong, Minseo Kim, Seunghee Cha, Kyudong Han","doi":"10.1007/s13258-025-01634-x","DOIUrl":"10.1007/s13258-025-01634-x","url":null,"abstract":"<p><p>Bacterial 16S rRNA genes are widely used to classify bacterial communities within interesting environments (e.g., plants, water, human body) because they contain nine hyper-variable regions (V1-V9) reflecting a large number of sequence variation sites between species. Short-read sequencing platform (targeting partial region of 16S rRNA gene; approximately 150-500 bp) commonly used in the 16S-based microbiome study is favored by many researchers because it is economical and can generate highthroughput sequencing data faster than long-read sequencing platforms. However, this sequencing platform has technical limitations in that it cannot clarify bacterial classification at the species level compared to long-read sequencing technology, which can cover the unclassification issue due to sequence similarity between species by targeting the 16S full-length region. In recent microbiome research-related industries, species-level high-resolution microbial classification is considered a key challenge to secure microbial resources among institutions in the field. However, the long-read sequencing platforms currently offered are still under price adjustment (demanding higher cost than short-read sequencing platforms) and have the disadvantage of low base-calling accuracy compared to short-read sequencing platforms. Therefore, this brief communication introduces the'Molecular diagnosis-based bacterial classification' technology to predict candidate species by backtracking for unclassified bacterial taxonomy at the species level in the NGS-based 16S microbiome study.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"503-508"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669545","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":"Extracellular nicotinamide phosphoribosyltransferase visfatin activates JAK2-STAT3 pathway in cancer-associated fibroblasts to promote colorectal cancer metastasis.","authors":"Yun Lei, Dan Shu, Jianyu Xia, Tao Zhang, He Wei","doi":"10.1007/s13258-024-01596-6","DOIUrl":"10.1007/s13258-024-01596-6","url":null,"abstract":"<p><strong>Background: </strong>Metastasis is one of the major challenges in the treatment of colorectal cancer (CRC), during which cancer-associated fibroblasts (CAFs) in the tumor microenvironment are critically involved.</p><p><strong>Objective: </strong>In this study, we aim to explore the regulatory role of extracellular nicotinamide phosphoribosyltransferase Visfatin and its impact on CRC metastasis.</p><p><strong>Methods: </strong>To examine the effect of visfatin on CAFs, human CRC tissue-derived CAFs were exposed to visfatin, and the expression of inflammatory factors, activation of JAK-STAT pathway and production of ROS in CAFs were assessed. To examine the effect of visfatin-treated CAFs on CRC metastasis, human CRC cell line SW480 or SW620 were cultured with the conditioned medium derived from visfatin-treated CAFs, and the invasion and migration ability of SW480 or SW620 cells were evaluated by transwell migration and matrigel invasion assays.</p><p><strong>Results: </strong>Our previous study found that visfatin, a secreted form of nicotinamide phosphoribosyltransferase that governs the rate-limiting step of NAD synthesis, promoted CRC metastasis. However, little is known about the effect of visfatin on CAFs. The conditioned medium derived from visfatin- treated CAFs promotes the migratory and invasive capability of CRC cells, and enhance lung metastasis in mouse model. Visfatin treatment stimulated the expression of a couple of inflammatory factors in CAFs, which was mediated by visfatin-induced activation of JAK- STAT pathway and accumulation of ROS. Inhibition of JAK-STAT pathway or neutralization of cellular ROS attenuated visfatin-mediated migration and invasion of CRC cells.</p><p><strong>Conclusions: </strong>The present work highlights a critical role of visfatin in the crosstalk between CRC cells and CAFs, which moonlight as a non-metabolic extracellular signal molecule to hijacks JAK-STAT pathway in CAFs to promote CRC metastasis.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"615-624"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791665","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}