Molecular biomedicine最新文献

{"title":"Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer.","authors":"Yixiang Gu, Ruifeng Yang, Yang Zhang, Miaomiao Guo, Kyle Takehiro, Ming Zhan, Linhua Yang, Hui Wang","doi":"10.1186/s43556-024-00239-2","DOIUrl":"10.1186/s43556-024-00239-2","url":null,"abstract":"<p><p>Cancer remains a leading cause of mortality globally and a major health burden, with chemotherapy often serving as the primary therapeutic option for patients with advanced-stage disease, partially compensating for the limitations of non-curative treatments. However, the emergence of chemotherapy resistance significantly limits its efficacy, posing a major clinical challenge. Moreover, heterogeneity of resistance mechanisms across cancer types complicates the development of universally effective diagnostic and therapeutic approaches. Understanding the molecular mechanisms of chemoresistance and identifying strategies to overcome it are current research focal points. This review provides a comprehensive analysis of the key molecular mechanisms underlying chemotherapy resistance, including drug efflux, enhanced DNA damage repair (DDR), apoptosis evasion, epigenetic modifications, altered intracellular drug metabolism, and the role of cancer stem cells (CSCs). We also examine specific causes of resistance in major cancer types and highlight various molecular targets involved in resistance. Finally, we discuss current strategies aiming at overcoming chemotherapy resistance, such as combination therapies, targeted treatments, and novel drug delivery systems, while proposing future directions for research in this evolving field. By addressing these molecular barriers, this review lays a foundation for the development of more effective cancer therapies aimed at mitigating chemotherapy resistance.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"2"},"PeriodicalIF":6.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of artificial intelligence in pandemic responses: from epidemiological modeling to vaccine development.","authors":"Mayur Suresh Gawande, Nikita Zade, Praveen Kumar, Swapnil Gundewar, Induni Nayodhara Weerarathna, Prateek Verma","doi":"10.1186/s43556-024-00238-3","DOIUrl":"10.1186/s43556-024-00238-3","url":null,"abstract":"<p><p>Integrating Artificial Intelligence (AI) across numerous disciplines has transformed the worldwide landscape of pandemic response. This review investigates the multidimensional role of AI in the pandemic, which arises as a global health crisis, and its role in preparedness and responses, ranging from enhanced epidemiological modelling to the acceleration of vaccine development. The confluence of AI technologies has guided us in a new era of data-driven decision-making, revolutionizing our ability to anticipate, mitigate, and treat infectious illnesses. The review begins by discussing the impact of a pandemic on emerging countries worldwide, elaborating on the critical significance of AI in epidemiological modelling, bringing data-driven decision-making, and enabling forecasting, mitigation and response to the pandemic. In epidemiology, AI-driven epidemiological models like SIR (Susceptible-Infectious-Recovered) and SIS (Susceptible-Infectious-Susceptible) are applied to predict the spread of disease, preventing outbreaks and optimising vaccine distribution. The review also demonstrates how Machine Learning (ML) algorithms and predictive analytics improve our knowledge of disease propagation patterns. The collaborative aspect of AI in vaccine discovery and clinical trials of various vaccines is emphasised, focusing on constructing AI-powered surveillance networks. Conclusively, the review presents a comprehensive assessment of how AI impacts epidemiological modelling, builds AI-enabled dynamic models by collaborating ML and Deep Learning (DL) techniques, and develops and implements vaccines and clinical trials. The review also focuses on screening, forecasting, contact tracing and monitoring the virus-causing pandemic. It advocates for sustained research, real-world implications, ethical application and strategic integration of AI technologies to strengthen our collective ability to face and alleviate the effects of global health issues.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"1"},"PeriodicalIF":6.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calpain 2 promotes Lenvatinib resistance and cancer stem cell traits via both proteolysis-dependent and independent approach in hepatocellular carcinoma.","authors":"Xiaolu Ma, Kaixia Zhou, Tianqing Yan, Ling Hu, Suhong Xie, Hui Zheng, Ying Tong, Heng Zhang, Yanchun Wang, Zhiyun Gong, Cuncun Chen, Yanan Tian, Lin Guo, Renquan Lu","doi":"10.1186/s43556-024-00242-7","DOIUrl":"10.1186/s43556-024-00242-7","url":null,"abstract":"<p><p>Lenvatinib, an approved first-line regimen, has been widely applied in hepatocellular carcinoma (HCC). However, clinical response towards Lenvatinib was limited, emphasizing the importance of understanding the underlying mechanism of its resistance. Herein, we employed integrated bioinformatic analysis to identify calpain-2 (CAPN2) as a novel key regulator for Lenvatinib resistance in HCC, and its expression greatly increased in both Lenvatinib-resistant HCC cell lines and clinical samples. Further in vitro and in vivo experiments indicated that knocking down CAPN2 greatly sensitized HCC cells to Lenvatinib treatment, while overexpression of CAPN2 achieved opposite effects in a Lenvatinib-sensitive HCC cell line. Interestingly, we observed a close relationship between CAPN2 expression and cancer stem cell (CSC) traits in HCC cells, evidenced by impaired sphere-forming and CSC-related marker expressions after CAPN2 knockdown, and verse vice. Mechanistically, we strikingly discovered that CAPN2 exerted its function by both enzyme-dependent and enzyme-independent manner simultaneously: activating β-Catenin signaling through its enzyme activity, and preventing GLI1/GLI2 degradation through direct binding to YWHAE in an enzyme-independent manner, which disrupting the association between YWHAE and GLI1/GLI2 to inhibit YWHAE-induced degradation of GLIs. Notably, further co-immunoprecipitation assays revealed that YWHAE could promote the protein stability of CAPN2 via recruiting a deubiquitinase COPS5 to prevent ubiquitination-induced degradation of CAPN2. In summary, our data demonstrated that CAPN2 promoted Lenvatinib resistance via both catalytic activity-dependent and -independent approaches. Reducing CAPN2 protein rather than inhibiting its activity might be a promising strategy to improve Lenvatinib treatment efficiency in HCC.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"74"},"PeriodicalIF":6.3,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigallocatechin-3-gallate therapeutic potential in human diseases: molecular mechanisms and clinical studies.","authors":"Manzar Alam, Mehak Gulzar, Mohammad Salman Akhtar, Summya Rashid, Zulfareen, Tanuja, Anas Shamsi, Md Imtaiyaz Hassan","doi":"10.1186/s43556-024-00240-9","DOIUrl":"10.1186/s43556-024-00240-9","url":null,"abstract":"<p><p>Green tea has garnered increasing attention across age groups due to its numerous health benefits, largely attributed to Epigallocatechin 3-gallate (EGCG), its key polyphenol. EGCG exhibits a wide spectrum of biological activities, including antioxidant, anti-inflammatory, antibacterial, anticancer, and neuroprotective properties, as well as benefits for cardiovascular and oral health. This review provides a comprehensive overview of recent findings on the therapeutic potential of EGCG in various human diseases. Neuroprotective effects of EGCG include safeguarding neurons from damage and enhancing cognitive function, primarily through its antioxidant capacity to reduce reactive oxygen species (ROS) generated during physiological stress. Additionally, EGCG modulates key signaling pathways such as JAK/STAT, Delta-Notch, and TNF, all of which play critical roles in neuronal survival, growth, and function. Furthermore, EGCG is involved in regulating apoptosis and cell cycle progression, making it a promising candidate for the treatment of metabolic diseases, including cancer and diabetes. Despite its promising therapeutic potential, further clinical trials are essential to validate the efficacy and safety of EGCG and to optimize its delivery to target tissues. While many reviews have addressed the anticancer properties of EGCG, this review focuses on the molecular mechanisms and signaling pathways by which EGCG used in specific human diseases, particularly cancer, neurodegenerative and metabolic diseases. It serves as a valuable resource for researchers, clinicians, and healthcare professionals, revealing the potential of EGCG in managing neurodegenerative disorders, cancer, and metabolic diseases and highlighting its broader therapeutic values.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"73"},"PeriodicalIF":6.3,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling immune cell-related gene features and immunoregulatory ceRNA in ischemic stroke.","authors":"Yanbo Li, Sicheng Liu, Linda Wen, Linzhu Zhang, Xue Lei, Yaguang Zhang, Lei Qiu, Li He, Junhong Han","doi":"10.1186/s43556-024-00237-4","DOIUrl":"10.1186/s43556-024-00237-4","url":null,"abstract":"<p><p>Molecules in immune cells plays a vital role in the pathogenesis of ischemic stroke (IS). The aim of this study is to profile the landscape of molecules on the basis of immune cells in IS peripheral blood and construct an immunoregulatory competing endogenous RNA (ceRNA) network. We collected and combined multiple public transcriptome datasets from the peripheral blood of IS patients and healthy controls. CIBERSORT deconvolution revealed that the proportions of CD8 and CD4 naive T cells, monocytes, and neutrophils changed significantly in the IS group. Intersecting the immune cell-related genes identified by weighted gene co-expression network analysis (WGCNA) and differential expression analysis, 38 overlapping candidate biomarkers were selected. Three machine learning algorithms, including least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), and random forest were applied, and 11 distinct immune cell-related genes were identified. We obtained the mRNA-miRNA and miRNA-lncRNA interactions from StarBase v3.0, and constructed a ceRNA network based on the differentially expressed mRNAs, miRNAs, and lncRNAs. The aberrant expression of HECW2-centered ceRNAs in the peripheral blood of in-house patients was validated using quantitative PCR. We also revealed that the expression of HECW2 was positively correlated with lncRNAs LINC02593 through miRNAs miR-130a-3p, miR-130b-3p and miR-148b-3p in cells. These results show that there are distinct immune features between IS patients and healthy controls. The ceRNA network may help elucidate the mechanism of immune cell-related genes in IS and may serve as a therapeutic target.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"72"},"PeriodicalIF":6.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metastasis-associated lung adenocarcinoma transcript 1 overexpression in testis contributes to idiopathic non-obstructive azoospermia via repressing ETS variant transcription factor 5.","authors":"Lei Wei, Zonggang Feng, Qian Dou, Pengfen Li, Xinghua Zhao, Bin Hao","doi":"10.1186/s43556-024-00235-6","DOIUrl":"10.1186/s43556-024-00235-6","url":null,"abstract":"<p><p>Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), is a long non-coding RNA localized in the cell nucleus, known for its multifunctional roles, including potential involvement in spermatogenesis. This study investigates the mechanism by which MALAT1 dysregulation contributes to the pathogenesis of idiopathic non-obstructive azoospermia (iNOA). We analyzed MALAT1 levels in two gene expression profiling datasets comprising patients with obstructive azoospermia (OA) who have normal spermatogenesis and 13 patients with iNOA. The dysregulation of MALAT1 along with the expression levels of its negatively correlated genes were confirmed in a larger cohort of 24 OA patients and 38 iNOA patients. We examined the effects of MALAT1 overexpression in primary human spermatogonial stem cells (SSCs) and Sertoli cells. Additionally, we assessed DNA methylation, as well as levels of H3K27me3 and H3K27Ac level near the etv5 promoter region using ChIP-qPCR. We observed that MALAT1 was overexpressed in testes of iNOA patients with its levels negatively correlating with six spermatogenesis related genes and positively correlated with three others. Overexpression of MALAT1 in SSCs repressed proliferation and induced apoptosis while also suppressing ETS variant transcription factor 5 (ETV5) expression by promoting H3K27 tri-methylation of the ETV5 promoter. Overexpression of MALAT1 in Sertoli cells did not induce apoptosis but impaired their cell supporting function. In conclusion, MALAT1 overexpression in SSCs contributes to the pathogenesis of iNOA via downregulating ETV5 expression and promoting cell apoptosis.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"71"},"PeriodicalIF":6.3,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer-associated fibroblasts: heterogeneity, tumorigenicity and therapeutic targets.","authors":"Keke Lv, Tianlin He","doi":"10.1186/s43556-024-00233-8","DOIUrl":"10.1186/s43556-024-00233-8","url":null,"abstract":"<p><p>Cancer, characterized by its immune evasion, active metabolism, and heightened proliferation, comprises both stroma and cells. Although the research has always focused on parenchymal cells, the non-parenchymal components must not be overlooked. Targeting cancer parenchymal cells has proven to be a formidable challenge, yielding limited success on a broad scale. The tumor microenvironment(TME), a critical niche for cancer cell survival, presents a novel way for cancer treatment. Cancer-associated fibroblast (CAF), as a main component of TME, is a dynamically evolving, dual-functioning stromal cell. Furthermore, their biological activities span the entire spectrum of tumor development, metastasis, drug resistance, and prognosis. A thorough understanding of CAFs functions and therapeutic advances holds significant clinical implications. In this review, we underscore the heterogeneity of CAFs by elaborating on their origins, types and function. Most importantly, by elucidating the direct or indirect crosstalk between CAFs and immune cells, the extracellular matrix, and cancer cells, we emphasize the tumorigenicity of CAFs in cancer. Finally, we highlight the challenges encountered in the exploration of CAFs and list targeted therapies for CAF, which have implications for clinical treatment.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"70"},"PeriodicalIF":6.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircMYH9/miR-133a-3p/CXCR4 axis: a novel regulatory network in sperm fertilization and embryo development.","authors":"Qian Sun, Yanyu Li, Wen Yang, Wen Feng, Jiayun Zhou, Yijuan Cao, Bei Zhang, Zuobin Zhu, Conghui Han","doi":"10.1186/s43556-024-00236-5","DOIUrl":"10.1186/s43556-024-00236-5","url":null,"abstract":"<p><p>This study aimed to investigate the influence of sperm miRNAs on fertilization rates (FR) in in vitro fertilization (IVF) and to explore potential regulatory mechanisms in sperm-mediated fertilization and embryo development. Through high-throughput sequencing, we identified differentially expressed miRNAs in sperm, with miR-133a-3p significantly upregulated in samples associated with low FR and available embryo rate (AER). Key regulatory circRNAs and mRNAs were further identified via the Starbase database, intersected with differentially expressed RNA, and analyzed through GO, KEGG, and PPI analyses. The circMYH9/miR-133a-3p/CXCR4 axis emerged as a critical regulatory network. In vitro assays using the GC-2 spd mouse spermatogenic cell line revealed that miR-133a-3p inhibited cell growth and proliferation while promoting apoptosis. circMYH9, acting as a competing endogenous RNA (ceRNA) for miR-133a-3p, modulated CXCR4 expression, enhancing GC-2 spd cell growth and inhibiting apoptosis through the miR-133a-3p/CXCR4 axis. In vivo experiments using a mouse model confirmed that circMYH9 overexpression increased IVF success rates and promoted embryo development via this axis. Mechanistically, miR-133a-3p suppresses sperm fertilization and embryo development by targeting the circMYH9/miR-133a-3p/CXCR4 axis. These findings suggest that this regulatory network could serve as a novel biomarker for assessing fertilization potential and embryo quality in clinical settings and as a potential therapeutic target to improve IVF outcomes and address infertility. This study provides valuable insights into the molecular mechanisms governing sperm function and early embryonic development.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"69"},"PeriodicalIF":6.3,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pentraxin-3 modulates hepatocyte ferroptosis and the innate immune response in LPS-induced liver injury.","authors":"Huitong Wang, Zhaojie Su, Yunyun Qian, Baojie Shi, Hao Li, Wenbin An, Yi Xiao, Cheng Qiu, Zhixiang Guo, Jianfa Zhong, Xia Wu, Jiajia Chen, Ying Wang, Wei Zeng, Linghui Zhan, Jie Wang","doi":"10.1186/s43556-024-00227-6","DOIUrl":"10.1186/s43556-024-00227-6","url":null,"abstract":"<p><p>The liver plays a crucial role in the immune response during endotoxemia and is one of the critical targets for sepsis-related injuries. As a secretory factor involved in inflammation, pentraxin-3 (PTX3) has been demonstrated to regulate hepatic homeostasis; however, the relationship between PTX3 and cell crosstalk between immune cells and hepatocytes in the liver remains incompletely understood. In this study, we revealed that, compared with WT mice, Ptx3^-/- mice with lipopolysaccharide (LPS)-induced endotoxemia exhibited alleviated liver damage, with reduced serum alanine transaminase and aspartate transaminase levels and an improved survival rate. Mechanistically, RNA-Seq and western blot results revealed that Ptx3 knockdown in hepatocytes increased the expression of Tfrc and Ccl20; consequently, Ptx3 deficiency regulated LPS-induced hepatocyte ferroptosis via increased mitochondrial reactive oxygen species and Fe²⁺ and recruited more macrophages by CCL20/CCR6 axis to be involved in inflammation and the clearance of harmful substances. Moreover, western blot and immunofluorescence staining confirmed that the NF-κB signaling pathway was upregulated upon LPS treatment in Ptx3-knockdown macrophages, promoting phagocytosis and polarization toward M1 macrophages. Collectively, our findings show that the absence of Ptx3 can ameliorate sepsis-induced liver injury by regulating hepatocyte ferroptosis and promote the recruitment and polarization of M1 macrophages. These findings offer a key basis for the development of effective treatments for acute infections.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"68"},"PeriodicalIF":6.3,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetyltransferase NAT10 promotes an immunosuppressive microenvironment by modulating CD8⁺ T cell activity in prostate cancer.","authors":"Ji Liu, Zhuoran Gu, Libin Zou, Zhijin Zhang, Liliang Shen, Ruiliang Wang, Shaobo Xue, Jiang Geng, Shiyu Mao, Wentao Zhang, Xudong Yao","doi":"10.1186/s43556-024-00228-5","DOIUrl":"10.1186/s43556-024-00228-5","url":null,"abstract":"<p><p>N-acetyltransferase 10 (NAT10), an enzyme responsible for ac4C acetylation, is implicated in cancer progression, though its specific biological function in prostate cancer remains insufficiently understood. This study clarifies NAT10's role in prostate cancer and its effects on the tumor immune microenvironment. NAT10 expression and clinical relevance were assessed through bioinformatics, RT-qPCR, and IHC analyses, comparing prostate cancer tissues with normal controls. The impact of NAT10 on tumor cell proliferation, migration, and invasion was investigated via in vitro assays-including CCK-8, EdU, wound healing, and 3D-Transwell-as well as in vivo mouse xenograft models and organoid studies. Further, NAT10's influence on immune cell infiltration was examined using flow cytometry, IHC, cell co-culture assays, and ELISA to elucidate downstream chemokine effects, specifically targeting CD8⁺ T cells. Findings indicated significant upregulation of NAT10 in prostate cancer cells, enhancing their proliferative and invasive capacities. Notably, NAT10 suppresses CD8⁺ T cell recruitment and cytotoxicity through the CCL25/CCR9 axis, fostering an immunosuppressive microenvironment that exacerbates tumor progression. An ac4C modification score was also devised based on NAT10's downstream targets, providing a novel predictive tool for evaluating immune infiltration and forecasting immunotherapy responses in patients with prostate cancer. This study underscores NAT10's pivotal role in modulating the prostate cancer immune microenvironment, offering insights into the immune desert phenomenon and identifying NAT10 as a promising therapeutic target for improving immunotherapy efficacy.</p>","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"67"},"PeriodicalIF":6.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}