{"title":"siRNA Knocking Down in HepG2 Cells Identifies PFKFB4 and HNF4α as Key Genes Important for Cancer Cell Survival.","authors":"Amer Imraish, Walhan Alshaer, Tuqa Abu-Thiab, Fatima Enaya, Hamzeh J Al-Ameer, Afnan Al-Hunaiti, Mohammad Abumurad, Malek Zihlif","doi":"10.2174/0115665232337735250101121115","DOIUrl":"https://doi.org/10.2174/0115665232337735250101121115","url":null,"abstract":"<p><strong>Introduction: </strong>Liposomes are versatile delivery systems for encapsulating small interfering RNAs (siRNAs) because they enhance cellular uptake and gene silencing. This study compares the new liposome formula to commercial lipofectamine in delivering siRNAs targeting hepatic carcinoma genes, focusing on HNF4-α and PFKFB4.</p><p><strong>Methods: </strong>Flow cytometry and confocal microscopy revealed efficient internalization of PE-Rhod- B labeled lipoplexes in HepG2 cells, while cytotoxicity assays demonstrated significant reductions in cell viability, particularly with siHNF4-α and siPFKFB4.</p><p><strong>Results: </strong>The newly formulated liposomes showed superior efficacy, achieving nearly 93% cytotoxicity at 100 nM, compared to just 50% with lipofectamine at the same concentration. Furthermore, real-time PCR confirmed that the liposome-encapsulated siHNF4-α reduced HNF4-α mRNA expression by tenfold at 100 nM, compared to a twofold reduction with lipofectamine at 200 nM. Similarly, siPFKFB4 delivered via liposomes showed a dose-dependent 35-fold reduction in PFKFB4 mRNA expression at 100 nM, outperforming the maximum reduction achieved by lipofectamine. The IC50 values for all siRNA treatment groups were significantly lower when using the liposome formula, reflecting improved delivery efficiency.</p><p><strong>Conclusion: </strong>These results demonstrate the potential of liposome formulations for therapeutic siRNA delivery. The encapsulation enhances cellular uptake and gene silencing efficiency, making the liposome formula a promising candidate for targeted gene therapy in hepatic carcinoma. Further research should explore it's in vivo biodistribution and potential combination therapies.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current gene therapyPub Date : 2025-01-13DOI: 10.2174/0115665232332412241118063211
Yasemin van Heuvel, Jörn Stitz
{"title":"Development of Lentiviral Packaging Cells and Scale Up of Production to Meet the Growing Demand in Cell and Gene Therapy.","authors":"Yasemin van Heuvel, Jörn Stitz","doi":"10.2174/0115665232332412241118063211","DOIUrl":"https://doi.org/10.2174/0115665232332412241118063211","url":null,"abstract":"<p><p>Gamma-Retroviral (RVVs) and lentiviral vectors (LVVs) represent indispensable tools in somatic gene therapy, mediating the efficient, stable transfer of therapeutic genes into a variety of human target cells. LVVs, in contrast to RVVs, are capable of stably genetically modifying non-proliferating target cells, making them the superior instrument in cell and gene therapy. To date, the LVV manufacturing process employs human embryonic kidney cells (HEK293) and derivatives thereof transiently transfected with multiple plasmids encoding the required viral vector components. Alternatively, stable packaging cell lines were developed and engineered to express all vector components in trans. Currently, these cells are mostly cultured in cell stacks, where they grow adherently in 2D layers, limiting the scale-up of vector production. The production of viral vectors using stable suspension cell lines enables larger-scale production and higher yields under controlled conditions. Here, we review the improvements made to enhance vector safety and production yield. Current advancements in the establishment of stable packaging cell lines enabling inducible and constitutive LVV production are summarized and discussed. Manufacturing processes for lentiviral vectors using bioreactors with perfusion systems are required to meet the growing demand in cell and gene therapy and to reduce production and therapy costs.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current gene therapyPub Date : 2025-01-10DOI: 10.2174/0115665232335957241122164034
André Miguel Martinez Júnior, Vera Aparecida de Oliveira, Marcio José Tiera
{"title":"O-substituted Tertiary Amine-chitosans as Promising Nanocarriers for siRNA Delivery.","authors":"André Miguel Martinez Júnior, Vera Aparecida de Oliveira, Marcio José Tiera","doi":"10.2174/0115665232335957241122164034","DOIUrl":"https://doi.org/10.2174/0115665232335957241122164034","url":null,"abstract":"<p><strong>Introduction: </strong>The clinical translation of chitosan-based formulations for siRNA delivery has been partially limited by their poor stability/solubility at physiological conditions, although they have good biocompatibility and cost-effectiveness.</p><p><strong>Method: </strong>In this study, the chitosan was O-substituted with diisopropylethylamine (DIPEA) groups, which improved its solubility at pH 7.4 by increasing the degree of ionization and enhanced the ability of chitosan to load siRNA at very low amine/phosphate (N/P) ratios. The O-DIPEAchitosan/ siRNA nanopolyplexes were self-assembled by complexation and presented positive Zeta potentials (ζ = +8 to +10 mV), spherical-like morphology, 200-300 nm size, low polydispersity index (PDI < 0.2), and were able to protect the siRNA from degradation by RNAse. Also, the resistance to albumin-induced disassembly and aggregation revealed both good structural and colloidal stabilities of the siRNA nanopolyplexes.</p><p><strong>Result: </strong>The nanopolyplexes displayed low cytotoxicities in RAW 264.7 macrophages and were successfully uptaken by both macrophages and HeLa cells achieving internalization efficiency similar to Lipofectamine. A positive correlation was observed between the physicochemical properties of the siRNA nanocarrier and its transfection efficiency.</p><p><strong>Conclusion: </strong>A knockdown of about 60-70% of tumor necrosis factor alpha (TNFα) was reached in lipopolysaccharide-stimulated macrophages treated with O-DIPEA-chitosan/siTNFα nanopolyplexes. Overall, the results confirmed that O-DIPEA chitosans are promising carriers for siRNA delivery.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current gene therapyPub Date : 2025-01-08DOI: 10.2174/0115665232327174241211075019
Prankur Awasthi, Arjun Singh Kohli, Manish Dwivedi, Saba Hasan
{"title":"Implications of EBV-Encoded and EBV-Related miRNAs in Tumors.","authors":"Prankur Awasthi, Arjun Singh Kohli, Manish Dwivedi, Saba Hasan","doi":"10.2174/0115665232327174241211075019","DOIUrl":"https://doi.org/10.2174/0115665232327174241211075019","url":null,"abstract":"<p><p>Over 90% of people are infected with the human g-herpesvirus known as the Epstein- Barr virus (EBV). Cancers, such as gastric carcinoma, non-Hodgkin's lymphoma, nasopharyngeal carcinoma, Hodgkin's lymphoma, and Burkitt lymphoma, are thought to be linked with EBV. It is noteworthy that the first virus discovered that encodes microRNAs (miRNAs) was EBV, and these miRNAs show expression at the different phases of EBV infection. There is growing evidence that EBV-encoded miRNAs influence the growth of EBV-associated tumors. These EBV miRNAs, i.e., BamHI-H rightward fragment 1-derived microRNAs (BHRF1miRNA) and BamHI-A rightward fragment-derived microRNAs (BART miRNAs), are crucial for the persistence of viral infection and the avoidance of host defenses. Currently, significant advancements have been made in analyzing the microRNAs that are found in the duration of EBV infection, in vitro studies identified molecular targets of miRNAs and in vivo studies enhanced our understanding regarding the pathophysiology of these molecules. An extensive look into the pro-carcinogenic impact of microRNAs associated with EBV will increase our understanding of the molecular mechanisms of EBV-associated tumors. In this paper, we have highlighted the functions of miRNAs in EBV infection as well as recent developments in miRNA-based therapeutic and diagnostic approaches that could be useful for EBV-related malignancies. Significantly, targeted therapies against EBV miRNAs are advancing rapidly, with emerging approaches such as miRNA sponges, anti-miRNA oligonucleotides, and CRISPR/Cas9 technologies. These innovations indicate the imminent onset of a new era in the treatment of EBV-associated tumors.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current gene therapyPub Date : 2025-01-07DOI: 10.2174/0115665232338503241227111640
Atabak Naiyeri, Amin Moqadami, Mohammad Khalaj-Kondori
{"title":"Untangling the Genetic Threads of Alzheimer's: Insights into Risk Factors and Biomarkers.","authors":"Atabak Naiyeri, Amin Moqadami, Mohammad Khalaj-Kondori","doi":"10.2174/0115665232338503241227111640","DOIUrl":"https://doi.org/10.2174/0115665232338503241227111640","url":null,"abstract":"<p><p>Dementia is a comprehensive term that refers to illnesses characterized by a decline in cognitive memory and other cognitive functions, affecting a person's overall ability to operate. The exact causes of dementia are unknown to this day. The heterogeneity of Alzheimer's indicates the contribution of genetic polymorphism to this disease. This disease is the most prevalent and damaging illness. Studies indicate that the global prevalence of Alzheimer's disease (AD) exceeds 26 million individuals. Investigation of variations in many genes indicates that these variations may be linked to the susceptibility to AD. Additional genetic factors could potentially influence AD. Analysis of several single-nucleotide polymorphisms in this context reveals a correlation between certain variants and AD. Regardless, Alzheimer's disease is always influenced by a particular APOE gene allele. The study's findings indicate that risk of Alzheimer's disease (AD) is linked to polymorphisms in the following genes: BDNF, presenilin-1 (PS-1), presenilin-2 (PS-2), LRP, APP, CTSD,5-6HT, TREM2, TNF-α, LPL, Clusterin (CLU), SORL1 (Sortilin-Related Receptor), PICALM, Complement Receptor 1 (CR1), and APOE genes.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CRISPR/Cas System: A Powerful Strategy to Improve Monogenic Human Diseases as Therapeutic Delivery; Current Applications and Challenges.","authors":"Fatemeh Saberi, Zeinab Yousefi-Najafabadi, Forough Shams, Zeinab Dehghan, Sepideh Ahmadi, Tayyebeh Pilehchi, Effat Noori, Zeinab Esmaeelzadeh, Maryam Bazgiri, Rezvan Mohammadi, Farzaneh Khani, Marzieh Sameni, Parisa Moradbeigi, Gholam Ali Kardar, Mohammad Salehi, Yong Teng, Vahid Jajarmi","doi":"10.2174/0115665232345516241119070150","DOIUrl":"https://doi.org/10.2174/0115665232345516241119070150","url":null,"abstract":"<p><p>The 5,000 to 8,000 monogenic diseases are inherited disorders leading to mutations in a single gene. These diseases usually appear in childhood and sometimes lead to morbidity or premature death. Although treatments for such diseases exist, gene therapy is considered an effective and targeted method and has been used in clinics for monogenic diseases since 1989. Monogenic diseases are good candidates for novel therapeutic technologies like gene editing approaches to repair gene mutations. Clustered regularly interspaced short palindromic repeats (CRISPR)-based systems, the pioneer and effective gene editing tool, are utilized for ex vivo and in vivo treatment of monogenic diseases. The current review provides an overview of recent therapeutic applications of CRISPR-based gene editing in monogenic diseases in in vivo and ex vivo models. Furthermore, this review consolidates strategies aimed at providing new treatment options with gene therapy, thereby serving as a valuable reference for advancing the treatment landscape for patients with monogenic disorders.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current gene therapyPub Date : 2025-01-06DOI: 10.2174/0115665232342293241120033251
Amrita Arup Roy, Rahul Pokale, Anoushka Mukharya, Ajinkya N Nikam, Kamal Dua, Bola Sadashiva Satish Rao, Raviraja Neelavar Seetharam, Srinivas Mutalik
{"title":"Synergizing CRISPR-Cas9 with Advanced Artificial Intelligence and Machine Learning for Precision Drug Delivery: Technological Nexus and Regulatory Insights.","authors":"Amrita Arup Roy, Rahul Pokale, Anoushka Mukharya, Ajinkya N Nikam, Kamal Dua, Bola Sadashiva Satish Rao, Raviraja Neelavar Seetharam, Srinivas Mutalik","doi":"10.2174/0115665232342293241120033251","DOIUrl":"https://doi.org/10.2174/0115665232342293241120033251","url":null,"abstract":"<p><p>The evolution of genetic exploration tools, from laborious methods like radiationinduced mutations to the transformative CRISPR-Cas9 system, has fundamentally reshaped genetic research and gene editing capabilities. This journey, initiated by foundational techniques such as ZFNs and TALENs and culminating in the groundbreaking work of Doudna and Charpentier in 2012, has ushered in an era of precise DNA alteration and profound insights into gene functions. The CRISPR/Cas9 system uses the Cas9 enzyme and guides RNA (gRNA) to precisely target and cleave DNA, with subsequent repair via error-prone NHEJ or precise HDR, enabling versatile gene editing. Complementary computational tools like E-CRISP and Azimuth 2.0, alongside advanced deep learning models like DeepCRISPR, have significantly contributed to refining CRISPR experiments, optimizing gRNA efficiency, and predicting outcomes with greater precision. In clinical applications, CRISPR-Cas9 shows great promise for treating complex genetic disorders like sickle cell disease and β-thalassemia, but faces challenges such as off-target effects, immune responses to viral vectors, and ethical issues in germline editing. Overcoming these challenges requires meticulous experimentation and robust regulatory frameworks to ensure responsible and beneficial utilization of the CRISPR-Cas9 technology across diverse fields, including cancer treatment, genetic disease therapies, agriculture, and synthetic biology, while continually addressing ethical, safety, and legal considerations for its advancement and widespread adoption.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current gene therapyPub Date : 2025-01-06DOI: 10.2174/0115665232340926241105064739
Chen Lu Li, Xin Yuan Ma, Ping Yi
{"title":"The Role of Immunotherapy in Lung Cancer Treatment: Current Strategies, Future Directions, and Insights into Metastasis and Immune Microenvironment.","authors":"Chen Lu Li, Xin Yuan Ma, Ping Yi","doi":"10.2174/0115665232340926241105064739","DOIUrl":"https://doi.org/10.2174/0115665232340926241105064739","url":null,"abstract":"<p><p>Lung cancer is a leading cause of mortality worldwide. Immunotherapy has emerged as a potentially effective strategy, as traditional medicines have shown minimal success. This review investigates the current state of immunotherapy for lung cancer treatment, focusing on its mechanisms, clinical applications, strategies, and future directions. This study focuses on the different characteristics of non-small and small-cell lung cancer to emphasize the need for targeted treatment strategies. In non-small cell lung cancer, immune checkpoint inhibitors that target PD-1, PDL1, and CTLA-4 have shown a strong therapeutic benefit and increased survival rates. The complex interactions among tumor cells, immune cells, and the tumor microenvironment significantly impact the outcome of immunotherapy. The determination of predicting biomarkers and conquering resistance requires an understanding of the tumor microenvironment. This study addresses a range of immunotherapeutic strategies, such as immune modulators, monoclonal antibodies, and cancer vaccines. The combination approaches are being explored to enhance treatment effectiveness and address resistance mechanisms that integrate immunotherapy with other modalities. Despite advancements, challenges still exist. The identification of reliable biomarkers, regulating immune- related adverse effects, and the overcoming of limitations in treating metastatic disease require more investigation. Future research directions should include exploring the immune microenvironment, developing personalized treatment strategies based on tumor profiles, and integrating new technologies for patient screening. Immunotherapy holds immense potential to modify lung cancer treatment and enhance clinical results.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current gene therapyPub Date : 2025-01-03DOI: 10.2174/0115665232257596231011110813
Zitong Wang, Ping Wang, Guoyou He, Liang Cheng, Tianyu Li, Yan Wang, Hong Li
{"title":"Identification of the Metabolic Characteristic of Organ Fibrosis Using Microbial Analysis on RNA-seq Data.","authors":"Zitong Wang, Ping Wang, Guoyou He, Liang Cheng, Tianyu Li, Yan Wang, Hong Li","doi":"10.2174/0115665232257596231011110813","DOIUrl":"https://doi.org/10.2174/0115665232257596231011110813","url":null,"abstract":"<p><strong>Background: </strong>Fibrosis refers to abnormal deposition of extracellular matrix, which leads to organ dysfunction. Metabolic alterations, especially enhanced glycolysis and suppressed fatty acid oxidation, are recognized as an essential pathogenic process of fibrosis. Recently, several reports indicate that the changes in microbiota composition are associated with metabolic disorders, suggesting microbes may contribute to organ fibrosis by regulating metabolic processes.</p><p><strong>Method: </strong>In this study, microbial reannotation was carried out on the RNA-seq data of fibrotic organs. Then, the microbial composition differences among healthy and fibrotic organ samples were determined by alpha and beta diversity analysis. Common and specific microbial markers of fibrosis were also identified by LEfSe. After that, the correlation analysis of the characteristic microbe-- gene-functional pathway was conducted to confirm the effects of microbes on host metabolism.</p><p><strong>Result: </strong>The results showed that the microbial composition significantly differed between healthy and diseased organs. Besides, the common characteristic microbes interacted closely with each other and contributed to fibrosis through symbiosis or inhibition. The largest proportion in fibrosis organs was Proteobacteria, which was the main source of pathogenic microbes.</p><p><strong>Conclusion: </strong>Further study found that the metabolic alteration driven by common and special characteristic microbes in fibrotic organs focused on the processes related to glycolysis and fatty acid metabolism.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current gene therapyPub Date : 2025-01-01DOI: 10.2174/0115665232291300240509104344
Wei Jiang, Sheng Xu, Ping Li
{"title":"SLC2A3 is a Potential Factor for Head and Neck Squamous Cancer Development through Tumor Microenvironment Alteration.","authors":"Wei Jiang, Sheng Xu, Ping Li","doi":"10.2174/0115665232291300240509104344","DOIUrl":"10.2174/0115665232291300240509104344","url":null,"abstract":"<p><strong>Introduction: </strong>Tumor immunity has garnered increasing attention in cancer treatment and progression. However, there is still a challenge in understanding the mechanisms of specific molecules affecting the clinical prognosis and tumor microenvironment (TME).</p><p><strong>Methods: </strong>Here, we applied the ESTIMATE algorithm to calculate the immune and stromal scores in 504 HNSC cases from TCGA. Patients were grouped according to the median value of the immune and stromal. Clinicopathological characteristics and differentially expressed genes (DEG) were analyzed. Subsequently, LASSO, COX regression, survival analysis, and clinicopathological characteristics were conducted. Subsequently, SLC2A3 was determined as a predictive factor that high expression of SLC2A3 at the mRNA and protein levels predicted a worse clinical prognosis. GSEA25099 was utilized for external validation of immune infiltration, while tissue PCR, IHC, and Western Blot were used to confirm the expression levels of SLC2A3.</p><p><strong>Results: </strong>A series of immune-infiltration analyses showed that SLC2A3 expression was negatively correlated with CD8+ T cells, significantly affecting the survival prognosis of HNSC. In the GSEA analysis, the high expression of SLC2A3 was mainly enriched for immune-related biological processes. Meanwhile, high expression of SLC2A3 possessed higher TIDE scores and was also strongly positively correlated with a series of immune checkpoints affecting survival prognosis, thus causing greater susceptibility to immune escape.</p><p><strong>Conclusion: </strong>Conclusively, SLC2A3 is a potential oncogene and factor of HNSC development, notably by an altered state of the immune microenvironment, immune-suppressive regulation, and immune escape.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"157-177"},"PeriodicalIF":3.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}