{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T20:40:56Z","timestamp":1770756056526,"version":"3.50.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Nucleosome assembly protein 1-like 5 (NAP1L5), a critical regulator of gene transcription and nucleosome assembly, has been implicated in the progression and poor prognosis of various cancers. However, its specific role and molecular mechanisms in acute myeloid leukemia (AML) remain largely unexplored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To identify key genes associated with AML, we analyzed gene expression profiles from AML patients and healthy controls using microarray datasets obtained from the GEO database. Differential expression analysis was performed to identify differentially expressed genes (DEGs), among which NAP1L5 emerged as a critical candidate based on its expression patterns and prognostic relevance, and we validated NAP1L5 expression in clinical AML samples. To elucidate the functional role of NAP1L5, we conducted Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) analysis, which revealed its involvement in specific signaling pathways and biological processes. Furthermore, we constructed an interaction network and predictive model for NAP1L5, complemented by an assessment of its role in immune infiltration and drug sensitivity. Finally, we conducted <jats:italic>in vitro<\/jats:italic> experiments to explore its biological functions and underlying molecular mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In AML, elevated expression of NAP1L5 was significantly associated with reduced overall survival, underscoring its prognostic relevance. GSEA revealed that NAP1L5 was prominently enriched in pathways related to apoptosis and DNA replication. GO analysis further indicated that its co-expressed genes were closely linked to autophagy and stress response mechanisms. Interaction network analysis revealed that NAP1L5 engages in complex regulatory interactions with multiple genes, miRNAs, transcription factors (TFs), and RNA-binding proteins (RBPs). Notably, high NAP1L5 expression correlated with increased infiltration of resting CD4+ memory T cells, implicating its potential influence on the tumor immune microenvironment. A predictive model integrating NAP1L5 expression and clinical AML features exhibited robust prognostic utility. Drug sensitivity analysis identified NAP1L5 overexpression as a marker of resistance to Zibotentan, along with associations with 49 additional therapeutic agents. <jats:italic>In vitro<\/jats:italic> functional assays demonstrated that NAP1L5 overexpression promoted cellular proliferation, migration, and colony formation while concurrently inhibiting apoptosis, highlighting its oncogenic potential in AML pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>NAP1L5 emerges as a promising prognostic biomarker and therapeutic target in AML, offering potential for improved patient outcomes and precision treatment strategies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1617564","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T04:10:58Z","timestamp":1753416658000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["NAP1L5 in acute myeloid leukemia: a prognostic biomarker and potential therapeutic target"],"prefix":"10.3389","volume":"15","author":[{"given":"Meng","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhibin","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqing","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Ge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2211429119","article-title":"Transcriptome-based molecular subtypes and differentiation hierarchies improve the classification framework of acute myeloid leukemia","volume":"119","author":"Cheng","year":"2022","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022016867","article-title":"Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN","volume":"140","author":"D\u00f6hner","year":"2022","journal-title":"Blood"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1902375116","article-title":"Heterogeneity in refractory acute myeloid leukemia","volume":"116","author":"Horibata","year":"2019","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2022.280801","article-title":"The clinical impact of the molecular landscape of acute myeloid leukemia","volume":"108","author":"Kayser","year":"2023","journal-title":"Haematologica"},{"key":"B5","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.blre.2019.04.005","article-title":"Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges","volume":"36","author":"Shallis","year":"2019","journal-title":"Blood Rev"},{"key":"B6","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1007\/s11864-020-00765-5","article-title":"Treatment of relapsed acute myeloid leukemia","volume":"21","author":"Thol","year":"2020","journal-title":"Curr Treat Options Oncol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.bbaexp.2003.09.012","article-title":"Histone chaperones, a supporting role in the limelight","volume":"1677","author":"Loyola","year":"2004","journal-title":"Biochim Biophys Acta"},{"key":"B8","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1111\/j.1365-2443.2009.01361.x","article-title":"Functional characterization of human nucleosome assembly protein 1-like proteins as histone chaperones","volume":"15","author":"Okuwaki","year":"2010","journal-title":"Genes Cells"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204377","article-title":"NAP1L5 targeting combined with MYH9 Inhibit HCC progression through PI3K\/AKT\/mTOR signaling pathway","volume":"14","author":"Zhao","year":"2022","journal-title":"Aging (Albany NY)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2023.115811","article-title":"NAP1L5 facilitates pancreatic ductal adenocarcinoma progression via TRIM29-mediated ubiquitination of PHLPP1","volume":"217","author":"Xiao","year":"2023","journal-title":"Biochem Pharmacol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e71","DOI":"10.1093\/nar\/gkv1507","article-title":"TCGAbiolinks: an R\/Bioconductor package for integrative analysis of TCGA data","volume":"44","author":"Colaprico","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0546-8","article-title":"Visualizing and interpreting cancer genomics data via the Xena platform","volume":"38","author":"Goldman","year":"2020","journal-title":"Nat Biotechnol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.11.014","article-title":"TIM-3 is a promising target to selectively kill acute myeloid leukemia stem cells","volume":"7","author":"Kikushige","year":"2010","journal-title":"Cell Stem Cell"},{"key":"B14","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1186\/s12885-019-5822-y","article-title":"Long non-coding RNA HOXB-AS3 promotes myeloid cell proliferation and its higher expression is an adverse prognostic marker in patients with acute myeloid leukemia and myelodysplastic syndrome","volume":"19","author":"Huang","year":"2019","journal-title":"BMC Cancer"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl887","article-title":"NCBI GEO: mining tens of millions of expression profiles\u2013database and tools update","volume":"35","author":"Barrett","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e33277","article-title":"Comprehensive Analysis of angiogenesis associated genes and tumor microenvironment infiltration characterization in cervical cancer","volume":"10","author":"Li","year":"2024","journal-title":"Heliyon"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1486961","article-title":"Identification and validation of mitophagy-related genes in acute myocardial infarction and ischemic cardiomyopathy and study of immune mechanisms across different risk groups","volume":"16","author":"Hao","year":"2025","journal-title":"Front Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0301-7_11","article-title":"Gene ontology semantic similarity analysis using GOSemSim","volume":"2117","author":"Yu","year":"2020","journal-title":"Methods Mol Biol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz757","article-title":"miRDB: an online database for prediction of functional microRNA targets","volume":"48","author":"Chen","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw965","article-title":"ChIPBase v2.0: decoding transcriptional regulatory networks of non-coding RNAs and protein-coding genes from ChIP-seq data","volume":"45","author":"Zhou","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.3643","article-title":"Exostosin1 as a novel prognostic and predictive biomarker for squamous cell lung carcinoma: A study based on bioinformatics analysis","volume":"10","author":"Wu","year":"2021","journal-title":"Cancer Med"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3337","article-title":"Robust enumeration of cell subsets from tissue expression profiles","volume":"12","author":"Newman","year":"2015","journal-title":"Nat Methods"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000001094","article-title":"Combining biomarker calibration data to reduce measurement error","author":"Perkins","year":"2019","journal-title":"Epidemiology"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e3181ec173d","article-title":"Receiver operating characteristic curve in diagnostic test assessment","volume":"5","author":"Mandrekar","year":"2010","journal-title":"J Thorac Oncol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1793","DOI":"10.1016\/j.jtcvs.2017.12.107","article-title":"Nomogram: An analogue tool to deliver digital knowledge","volume":"155","author":"Park","year":"2018","journal-title":"J Thorac Cardiovasc Surg"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/8201079","article-title":"Dichloroacetate (DCA) and cancer: an overview towards clinical applications","volume":"2019","author":"Tataranni","year":"2019","journal-title":"Oxid Med Cell Longev"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/sim.5958","article-title":"Estimating and comparing time-dependent areas under receiver operating characteristic curves for censored event times with competing risks","volume":"32","author":"Blanche","year":"2013","journal-title":"Stat Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1111","article-title":"Genomics of Drug Sensitivity in Cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells","volume":"41","author":"Yang","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022019056","article-title":"The palmitoyltransferase ZDHHC21 regulates oxidative phosphorylation to induce differentiation block and stemness in AML","volume":"142","author":"Shao","year":"2023","journal-title":"Blood"},{"key":"B33","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s13045-021-01062-w","article-title":"Emerging agents and regimens for AML","volume":"14","author":"Liu","year":"2021","journal-title":"J Hematol Oncol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.01.037","article-title":"The histone chaperone Nap1 promotes nucleosome assembly by eliminating nonnucleosomal histone DNA interactions","volume":"37","author":"Andrews","year":"2010","journal-title":"Mol Cell"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1101\/gr.781503","article-title":"Identification of novel imprinted genes in a genome-wide screen for maternal methylation","volume":"13","author":"Smith","year":"2003","journal-title":"Genome Res"},{"key":"B36","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1186\/s12885-023-11347-7","article-title":"MALAT1-regulated gene expression profiling in lung cancer cell lines","volume":"23","author":"Roh","year":"2023","journal-title":"BMC Cancer"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1172\/JCI149415","article-title":"Therapeutic targeting of BAG3: considering its complexity in cancer and heart disease","volume":"131","author":"Kirk","year":"2021","journal-title":"J Clin Invest"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2023.2201507","article-title":"Optimal combination of immune checkpoint and senescence molecule predicts adverse outcomes in patients with acute myeloid leukemia","volume":"55","author":"Wang","year":"2023","journal-title":"Ann Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-020-01199-3","article-title":"Deciphering molecular heterogeneity in pediatric AML using a cancer vs. normal transcriptomic approach","volume":"89","author":"Depreter","year":"2021","journal-title":"Pediatr Res"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1617564\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T04:10:59Z","timestamp":1753416659000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1617564\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,25]]},"references-count":39,"alternative-id":["10.3389\/fonc.2025.1617564"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1617564","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,25]]},"article-number":"1617564"}}