Gene最新文献

{"title":"RNA production of IgG receptors is present in podocytes and varies depending on glycemia – preliminary results on Fc gamma receptor presence in kidney cells","authors":"Marlena Typiak ,&nbsp;Aleksandra Sobczak ,&nbsp;Zofia Dobrzyńska ,&nbsp;Moin A. Saleem ,&nbsp;Anna Jaźwińska","doi":"10.1016/j.gene.2025.149501","DOIUrl":"10.1016/j.gene.2025.149501","url":null,"abstract":"<div><div>Diabetes results from high blood glucose level and is one of the four main noncommunicable diseases. It is also a major cause of kidney failure. An inflammation of renal tissue during diabetic kidney disease (DKD) is aimed to resolve the ongoing homeostatic imbalance, however it leads to renal tissue injury. Because, the kidney glomerulus, where the blood filtration occurs, is an immunologically privileged place with very few leukocytes within, it was suspected that cells within the glomerulus possess immunological features and may initiate or increase the inflammation of renal tissue. One of the cell types in glomerulus, podocytes, are not only crucial for plasma filtration, but also can phagocytose and were described as professional antigen presenting cells. Due to an increased level of IgG-based immune complexes generated in the blood of diabetic patients and deposited in their kidneys, it was also proposed, that podocytes may express receptors for Fc fragment of IgG (FcγRs), which initiate phagocytosis. Many analyses point to that, but it has never been tested before. Thus, in the current study, we have analyzed mRNA expression levels of FcγR-coding genes in human podocytes, compared it to their expression levels in other non-immune epithelial cells (ovarian cells) and to leukocytes, as well as compared FcγR-coding genes’ expression levels in podocytes cultured in a medium with standard versus high glucose concentration. The detection of FcγR expression in podocytes could help to understand the pathomechanism of renal tissue inflammation during DKD and subsequently help to prevent or minimize it.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"958 ","pages":"Article 149501"},"PeriodicalIF":2.6,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143830065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"De novo transcriptome assembly and functional annotation supports potential biotechnological applications for the non-model thraustochytrid Ulkenia visurgensis Lng2","authors":"Pedro Contreras ,&nbsp;Víctor Fica-León ,&nbsp;José Navarrete ,&nbsp;Claudia Oviedo","doi":"10.1016/j.gene.2025.149492","DOIUrl":"10.1016/j.gene.2025.149492","url":null,"abstract":"<div><div>Thraustochytrids are heterotrophic marine protists known for their ability to produce valuable lipids such as docosahexaenoic acid (DHA). However, like many non-model organisms, they present challenges for transcriptomic studies due to the limited reliable reference genomes and compatibility with curated protein databases, complicating the respective assembly and annotation. This study presents a <em>de novo</em> transcriptome assembly and functional annotation for the recently isolated thraustochytrid strain <em>Ulkenia visurgensis</em> Lng2 using solely free access software and code available in public domain repositories.</div><div>The assembled transcriptome presented 45,867 unique gene models, with a total of 66,623 transcripts and a contig N50 of 3162. Functional annotations highlighted high amounts of transcripts related to the biosynthesis of relevant lipidic molecules, as well as stress-adaptive features including catalytic and xenobiotic degrading activity. Likewise, 2381 transcripts were linked to enzymes with potential biotechnological applications. Notably, several transcripts corresponding to uncommon enzymatic activities in thraustochytrids, including laccases, cellulases, and chitinases, were identified. Additionally, evidence for a potential lactamase activity was found, marking the first report of such activity in thraustochytrids.</div><div>Overall, this study offers a simple free-access procedural strategy for a <em>de novo</em> transcriptome assembly and functional annotation in non-model organisms. These results provide valuable insights into the biotechnological potential of thraustochytrids, while also expanding the limited transcriptomic data available for these protists. Notably, it represents the first transcriptomic analysis of the <em>Ulkenia</em> genus.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"958 ","pages":"Article 149492"},"PeriodicalIF":2.6,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interallelic gene conversion of leukemia-associated single nucleotide variants","authors":"Alexander J. Silver ,&nbsp;Donovan J. Brown ,&nbsp;Sarah D. Olmstead ,&nbsp;Jackson M. Watke ,&nbsp;Agnieszka E. Gorska ,&nbsp;Londa Tanner ,&nbsp;Haley E. Ramsey ,&nbsp;Michael R. Savona","doi":"10.1016/j.gene.2025.149493","DOIUrl":"10.1016/j.gene.2025.149493","url":null,"abstract":"<div><div>CRISPR-Cas9 is a useful tool for inserting precise genetic alterations through homology-directed repair (HDR), although current methods largely rely on provision of an exogenous repair template. Here, we tested the possibility of interchanging heterozygous single nucleotide variants (SNVs) using mutation-specific guide RNA, and the cell’s own wild-type allele rather than an exogenous template. Using high-fidelity Cas9 to perform allele-specific CRISPR across multiple human leukemia cell lines as well as in primary hematopoietic cells from patients with leukemia, we find high levels of reversion to wild-type in the absence of exogenous template. Moreover, we demonstrate that bulk treatment to revert a truncating mutation in <em>ASXL1</em> using CRISPR-mediated interallelic gene conversion (IGC) is sufficient to prolong survival in a human cell line-derived xenograft model (median survival 33 days vs 27.5 days; <em>p</em> = 0.0040). These results indicate that IGC is a useful laboratory tool which can be applied to numerous types of leukemia and can meaningfully alter cellular phenotypes at scale. Because our method targets single-base mutations, rather than larger variants targeted by IGC in prior studies, it greatly expands the pool of genetic lesions which could potentially be targeted by IGC. This technique may reduce cost and complexity for experiments modeling phenotypic consequences of SNVs. The principles of SNV-specific IGC demonstrated in this proof-of-concept study could be applied to investigate the phenotypic effects of targeted clonal reduction of leukemogenic SNV mutations.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"958 ","pages":"Article 149493"},"PeriodicalIF":2.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lamb1-mediated Wnt/β-catenin signaling pathway drives endothelial angiogenesis for fracture healing","authors":"Yajun Yang ,&nbsp;Hangyu Li ,&nbsp;Zhirong Ma ,&nbsp;Zhiran Li ,&nbsp;Jinxin Gu","doi":"10.1016/j.gene.2025.149481","DOIUrl":"10.1016/j.gene.2025.149481","url":null,"abstract":"<div><h3>Objectives</h3><div>Fractures, usually caused by trauma or osteoporosis, are the most common traumatic injuries to large organs in humans. Osteogenesis and angiogenesis are two crucial parts of fracture healing that work together to promote the repair and regeneration of damaged bone. Endothelial cell migration is critical for angiogenesis. Therefore, it is well worth exploring whether endothelial cells (ECs) can enhance fracture healing.</div></div><div><h3>Methods</h3><div>The public datasets were analyzed by scRNA-seq, and the ECs were subjected to subset analysis and pseudotime analysis. Next, ECs_Lamb1⁺ cells underwent GO and KEGG pathway enrichment analyses, and were subjected to GSVA. Finally, the mechanism was verified and evaluated via qRT-PCR, cellular immunofluorescence staining, and transwell assay.</div></div><div><h3>Results</h3><div>After cell annotations, 9 cell types were obtained, and it was found that the proportions of ECs were significantly reduced. EC subset analysis showed that the ratio of ECs_Lamb1⁺ cells was significantly up-regulated in the Fracture group; pseudotime analysis showed that ECs_Lamb1^- cells were gradually reduced over time, whereas ECs_Lamb1⁺ cells were gradually expanding along the trajectories to reach a maximum at the end of the trajectory; pathway enrichment analyses revealed that ECs_Lamb1⁺ cells were mainly associated with several signaling pathways regulating cell proliferation, differentiation, repair, angiogenesis, and inflammatory responses, such as PI3K-Akt signaling pathway, Wnt/β-catenin, and MAPK. The results of basic assays demonstrated that successful knockdown of Lamb1 expression via siRNA-LAMB1 was detrimental to HUVEC proliferation, migration, and tube formation, and could suppress the expression of wnt3a, GSK-3β, β-catenin, and VEGFA; whereas, HY-141873 in combination with siRNA-LAMB1 partially reversed the down-regulated wnt3a, GSK-3β, β-catenin, and VEGFA expression, and HUVEC proliferation, migration, and tube formation were partially improved.</div></div><div><h3>Conclusion</h3><div>Lamb1 promotes fracture repair and healing by up-regulating VEGFA expression via the activation of Wnt signaling pathway to catalyze EC growth and migration and induce endothelial angiopoiesis.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"959 ","pages":"Article 149481"},"PeriodicalIF":2.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenicity analysis of three SCA14-associated missense mutations in PRKCG gene of Chinese patients with ataxia","authors":"Hongyu Yuan ,&nbsp;Zhao Chen ,&nbsp;Linlin Wan ,&nbsp;Linliu Peng ,&nbsp;Zhe Long ,&nbsp;Lang He ,&nbsp;Chunrong Wang ,&nbsp;Rong Qiu ,&nbsp;Beisha Tang ,&nbsp;Hong Jiang","doi":"10.1016/j.gene.2025.149483","DOIUrl":"10.1016/j.gene.2025.149483","url":null,"abstract":"<div><div>Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant disorder characterized by progressive cerebellar dysfunction and neurodegeneration. To date, it is rarely reported in China. SCA14 is caused by mutations in the <em>PRKCG</em> gene, which encodes protein kinase C gamma (PKCγ). Although nearly eighty distinct mutations of <em>PRKCG</em> gene have been identified, the pathological mechanisms of SCA14 remain unclear. In this study, we performed whole exome sequencing to screen causative genes in patients with unexplained progressive cerebellar ataxias, and identified three <em>PRKCG</em> mutations (c.302A &gt; G, p.H101R, c.520C &gt; G, p.H174D and c.2063C &gt; G, p.P688R) that have not been previously reported in Chinese patients with SCA14. To explore the pathogenicity and function of these SCA14-associated <em>PRKCG</em> mutations, HEK293T and HeLa cells were transfected with the plasmids of empty vector, wild-type <em>PRKCG</em> and indicated <em>PRKCG</em> mutants. Protein stability, aggregation propensity, phosphorylation status, mitochondrial function and cytotoxicity were then measured. We found that H101R mutant PKCγ protein is unstable, prone to aggregate, exhibits reduced basal phosphorylation, and is resistant to agonist-mediated dephosphorylation. Also, H101R mutant PKCγ protein could result in increased apoptosis and reduced cell viability. These findings are similar to other pathogenic mutations. Additionally, cellular mitochondrial dysfunction was observed for the first time in cells expressing mutant PKCγ. Together, we identified three <em>PRKCG</em> mutations, expanding the mutation spectrum of <em>PRKCG</em> in China. The c.302A &gt; G, p.H101R variant is pathogenic and mitochondrial dysfunction is suggested involved in the pathogenesis of SCA14.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"958 ","pages":"Article 149483"},"PeriodicalIF":2.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoy oligodeoxynucleotides targeting STATs in non-cancer gene therapy","authors":"Maryam Mahjoubin-Tehran ,&nbsp;Samaneh Rezaei ,&nbsp;Prashant Kesharwani ,&nbsp;Sercan Karav ,&nbsp;Amirhossein Sahebkar","doi":"10.1016/j.gene.2025.149482","DOIUrl":"10.1016/j.gene.2025.149482","url":null,"abstract":"<div><div>The Signal Transducer and Activator of Transcription (STAT) protein family is crucial for organizing the epigenetic configuration of immune cells and controlling various fundamental cell physiological functions including apoptosis, development, inflammation, immunological responses, and cell proliferation and differentiation. The human genome has seven known STAT genes, named 1, 2, 3, 4, 5a, 5b, and 6. Aberrant activation of STAT signaling pathways is associated with many human disorders, particularly cardiovascular diseases (CVDs), making these proteins promising therapeutic targets. Improved understanding of altered and pathological gene expression and its role in the pathophysiology of various hereditary and acquired disorders has enabled the development of novel treatment approaches based on gene expression modulation. One such promising development is the oligodeoxynucleotide decoy method, which may allow researchers to specifically influence gene activation or repression. Various oligodeoxynucleotide decoys target STATs and affect the expression of its downstream genes. We summarized cell culture and preclinical research, which evaluated the effects of oligodeoxynucleotide decoys target STATs in different types of non-cancer illnesses.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"957 ","pages":"Article 149482"},"PeriodicalIF":2.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allele-specific detection of isoniazid metabolism modulating variants of N-acetyltransferase 2 enzyme and their frequencies in the Bangladeshi population","authors":"Nabiha Tasneem Khan ,&nbsp;Md. Mahmudul Hasan Akash ,&nbsp;Abu Ashfaqur Sajib ,&nbsp;Sharif Akhteruzzaman","doi":"10.1016/j.gene.2025.149480","DOIUrl":"10.1016/j.gene.2025.149480","url":null,"abstract":"<div><div>Tuberculosis is one of the oldest diseases that still affects millions of people worldwide and remains a significant public health challenge. The N-acetyltransferase 2 (NAT2) enzyme metabolizes isoniazid (INH), a primary antibiotic in tuberculosis treatment. The single nucleotide polymorphisms (SNPs) of NAT2 affect the metabolism and function of isoniazid. The rs1801280 (T341C) and rs1208 (G803A) variants of NAT2 are associated with INH drug responses. Individuals with the slow-metabolizing rs1801280 variant of the NAT2 enzyme are at a higher risk of INH-induced liver damage and require lower doses or longer treatment regimens. At the same time, individuals with the fast-metabolizing rs1208 variant are at risk of treatment failure due to rapid drug metabolism. Genotyping of the NAT2 variants can help clinicians personalize tuberculosis treatment, optimize drug doses, and thus minimize adverse effects. Under this study, an allele-specific PCR (ASPCR) method was developed for genotyping the NAT2 variants, and the results were validated through targeted sequencing. The allele frequencies at the rs1801280 locus were 0.60 for the T allele and 0.40 for the C. For rs1208, the participants’ allele frequencies were 0.27 for the G allele and 0.73 for the A allele. This ASPCR method is quick, affordable, and could be used in routine genotyping to personalize the treatment for tuberculosis patients, leading to more effective and safer treatments. We also used molecular docking to study how the rs1801280 and rs1208 variants affect the interaction between the NAT2 enzyme and drugs. A slight change was visible in the flexibility of the amino acid residues. However, those amino acids were not involved in the ligand binding mechanism.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"957 ","pages":"Article 149480"},"PeriodicalIF":2.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the multifaceted role of nucleolin in cellular function and Cancer: Structure, Regulation, and therapeutic implications","authors":"Kruthika Prakash ,&nbsp;Srisri Satishkartik ,&nbsp;Satish Ramalingam ,&nbsp;Prakash Gangadaran ,&nbsp;S. Gnanavel ,&nbsp;K.N. Aruljothi","doi":"10.1016/j.gene.2025.149479","DOIUrl":"10.1016/j.gene.2025.149479","url":null,"abstract":"<div><div>Nucleolin (NCL), a highly conserved and multifunctional phosphoprotein, is primarily localized in the nucleolus and participates in various cellular compartments, including the nucleoplasm, cytoplasm, and plasma membrane. Initially discovered in the 1970 s, NCL is integral to ribosome biogenesis through its roles in ribosomal RNA transcription, processing, and assembly. Beyond ribosome synthesis, NCL plays critical roles in cellular processes such as DNA and RNA metabolism, chromatin remodeling, and cell cycle regulation, underscoring its essentiality for cell viability. Structurally, NCL comprises multiple functional domains, which facilitates interaction with various kinases and other proteins. NCL’s extensive post-translational modifications influence its localization and function. Importantly, NCL has emerged as a key player in multiple pathologies, particularly cancer, where it contributes to tumor growth, metastasis, and drug resistance. On the cell surface, NCL acts as a co-receptor for growth factors and other ligands, facilitating oncogenic signaling. Additionally, its regulation of non-coding RNAs, stabilization of oncogenic mRNAs, and involvement in immune evasion highlight its potential as a therapeutic target. This review provides an unexplored in-depth overview of NCL’s structure, functions, and modifications, with a focus on its role in cancer biology and its therapeutic implications.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"957 ","pages":"Article 149479"},"PeriodicalIF":2.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the role of extracellular vesicles in cervical cancer: Mechanisms of progression, resistance, and emerging therapeutic strategies","authors":"Michelle van der Merwe ,&nbsp;Kathy Myburgh ,&nbsp;Cathie Garnis ,&nbsp;Rebecca Towle ,&nbsp;Anna-Mart Engelbrecht","doi":"10.1016/j.gene.2025.149467","DOIUrl":"10.1016/j.gene.2025.149467","url":null,"abstract":"<div><div>Cervical cancer remains a significant global health challenge, particularly in its advanced stages, where treatment resistance complicates effective management. Extracellular vesicles (EVs) are crucial mediators of tumor progression and resistance, primarily through the transfer of miRNA cargo. In cervical cancer, specific miRNAs, including oncogenic miRNAs such as miR-21, miR-221-3p, miR-486-5p, and miR-92a-3p are upregulated in both cells and EVs, promoting proliferation, migration, epithelial-to-mesenchymal transition (EMT), and immune evasion—all of which contribute to therapy resistance and an aggressive tumor phenotype. Conversely, tumor-suppressive miRNAs, such as miR-122-5p, miR-100, and miR-142-3p, are selectively exported from cancer cells via EVs, suggesting a protective mechanism by which cancer cells eliminate these tumor suppressors. This review focuses on the role of oncogenic and tumor-suppressive miRNAs within EVs and their implications for cervical cancer progression and treatment resistance. Additionally, it examines the dynamic interactions between the tumor microenvironment (TME) and EV cargo, as well as emerging EV-based therapeutic strategies. These include the encapsulation of chemotherapeutic agents within EVs, the use of anti-miRs to silence oncogenic miRNAs, the delivery of tumor-suppressive miRNAs, the inhibition of EV release, and the targeting of downstream miRNA-regulated proteins. While miRNA-based therapies remain in the early stages, they hold significant promise for overcoming treatment resistance and improving cervical cancer outcomes.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"957 ","pages":"Article 149467"},"PeriodicalIF":2.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing NAPSA’s role in ccRCC: Insights from single-cell RNA sequencing","authors":"Zhichao Li ,&nbsp;Yuanjie Zhong ,&nbsp;Dan Ye ,&nbsp;Jincheng Yang ,&nbsp;Linbao Chen","doi":"10.1016/j.gene.2025.149478","DOIUrl":"10.1016/j.gene.2025.149478","url":null,"abstract":"<div><h3>Background</h3><div>Clear cell renal cell carcinoma (ccRCC) is aggressive and heterogeneous, resulting in poor prognosis due to frequent metastasis. Napsin A, an aspartic proteinase encoded by the NAPSA gene, is involved in protein processing and is expressed in the kidney and lung, but its function is not well understood. Studying ccRCC’s molecular characteristics, including Napsin A, is vital for enhancing diagnostics and treatment.</div></div><div><h3>Methods</h3><div>Single-cell RNA sequencing data from the GEO database (GSE210042) were analyzed, including seven tumor and two normal samples. The Seurat package was used for data preprocessing, clustering, and visualization. Differential expression and enrichment analyses were conducted between tumor and normal cells, and cell-to-cell communication was assessed between NAPSA + and NAPSA- cells. The correlation between NAPSA expression and EMT score was analyzed using TCGA-KIRC data. In vitro experiments involved transfecting OS-RC-2 and Caki-1 ccRCC cell lines with siRNA targeting NAPSA. Effect on the cellular EMT process induced by TGF-β1 was assessed by immunofluorescence staining.</div></div><div><h3>Results</h3><div>NAPSA was primarily expressed in podocytes and ccRCC epithelial cells, with significantly reduced levels in tumor tissues associated with poor prognosis. NAPSA downregulation may influence various biological pathways and enhance communication with tumor-associated macrophages and mast cells. Silencing NAPSA increased TGF-β1-induced epithelial-mesenchymal transition (EMT).</div></div><div><h3>Conclusion</h3><div>The study highlights NAPSA’s expression characteristics and potential role in ccRCC, suggesting it may serve as a biomarker. Further research is needed to elucidate NAPSA’s mechanisms and explore its applications in precision medicine.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"959 ","pages":"Article 149478"},"PeriodicalIF":2.6,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}