{ "abstract": "Background: Fatty acid binding protein 5 (FABP5) contributes to lipid metabolism and inflammation, but, its immunoregulatory role in hepatocellular carcinoma (HCC) is unclear. Considering the strong metabolic–immune interplay in HCC, elucidating how FABP5 shapes the tumor immune microenvironment may uncover new therapeutic targets. Methods: TCGA, CCLE and single-cell RNA-seq datasets were employed to characterize FABP5 expression and clinical relevance. FABP5 knockdown was performed to assess effects on HCC cell proliferation. Immune infiltration, immune checkpoint profiles, TIDE scores and enrichment of immune-related pathways were analyzed. Differentially expressed genes underwent GO and KEGG pathway enrichment analyses. Protein–protein docking, molecular dynamics (MD) simulations and in vitro assays were conducted to explore the regulatory role of FABP5 in the NF-κB/PD-L1 axis. Drug screening, molecular docking and duplicate MD simulations were carried out to identify potential FABP5-targeting compounds. Results: FABP5 was significantly upregulated in HCC and predicted worse survival, serving as an independent prognostic factor. Single-cell analysis identified predominant FABP5 expression in fibroblasts and macrophages. FABP5 knockdown suppressed cell proliferation, colony formation, DNA synthesis and migration, accompanied by decreased expression of epithelial–mesenchymal transition (EMT) markers. FABP5-high tumors exhibited increased immune infiltration but raised immune checkpoint levels and higher TIDE scores, indicative of an immunosuppressive microenvironment. FABP5 correlated positively with NF-κB pathway genes and molecular docking predicted stable complexes between IκBα and P65. Experimental validation confirmed that FABP5 drives PD-L1 upregulation in an NF-κB–dependent manner. Drug screening identified CZS-241 as the most promising FABP5-binding candidate, and duplicate MD simulations demonstrated a stable FABP5–CZS-241 complex. Conclusion: FABP5 drives immunosuppression in HCC by inducing PD-L1 via the NF-κB pathway. CZS-241 is identified as a promising FABP5-targeting compound with therapeutic potential for HCC.", "abstract_shown": true, "affiliations": [ "The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, People’s Republic of China", "The Affiliated Dongguan Songshan Lake Central Hospital, Guangdong Medical University, Dongguan, Guangdong, China", "Department of Acupuncture, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China", "Department of Radiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China", "Dongguan Key Laboratory of Traditional Chinese Medicine Hepatology, the Affiliated Dongguan Songshan Lake Central Hospital, Guangdong Medical University, Dongguan, China" ], "article_type": "Research Article", "arxiv": null, "author_total": 10, "authors": [ { "affs": [ 0 ], "name": "Rui An" }, { "affs": [ 1 ], "name": "Shibing Hou" }, { "affs": [ 2 ], "name": "Min Hong" }, { "affs": [ 3 ], "name": "Jiaorong Zhen" }, { "affs": [ 4 ], "name": "Zhijuan Wang" }, { "name": "Haoming Huang" }, { "name": "Weixuan Zhao" }, { "name": "Mianmian Liao" }, { "name": "Weiqu Yuan" }, { "name": "Danping Huang" } ], "bibtex": "https://research.draconitic.com/paper/57dhbabbp28wv.bib", "cited_by": 0, "doi": "10.1371/journal.pone.0356359", "fulltext_url": null, "id": "57dhbabbp28wv", "issns": [ "1932-6203" ], "landing_url": "https://doi.org/10.1371/journal.pone.0356359", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2730|Cancer Immunotherapy and Biomarkers" ], [ "plos", "/Biology and life sciences/Biochemistry/Biochemical simulations" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/DNA-binding proteins/Transcription factors" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/Regulatory proteins/Transcription factors" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/White blood cells/Macrophages" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/White blood cells/Macrophages" ], [ "plos", "/Biology and life sciences/Computational biology/Biochemical simulations" ], [ "plos", "/Biology and life sciences/Genetics/Gene expression/Gene regulation/Transcription factors" ], [ "plos", "/Biology and life sciences/Immunology/Immune cells" ], [ "plos", "/Biology and life sciences/Immunology/Immune cells/White blood cells/Macrophages" ], [ "plos", "/Medicine and health sciences/Gastroenterology and hepatology/Liver diseases/Hepatocellular carcinoma" ], [ "plos", "/Medicine and health sciences/Immunology/Immune cells" ], [ "plos", "/Medicine and health sciences/Immunology/Immune cells/White blood cells/Macrophages" ], [ "plos", "/Medicine and health sciences/Oncology/Cancers and neoplasms/Carcinoma/Hepatocellular carcinoma" ], [ "plos", "/Medicine and health sciences/Oncology/Cancers and neoplasms/Gastrointestinal tumors/Hepatocellular carcinoma" ], [ "plos", "/Medicine and health sciences/Pharmacology/Drugs/Immunosuppressives" ], [ "plos", "/Physical sciences/Chemistry/Computational chemistry/Molecular dynamics" ], [ "plos", "/Physical sciences/Physics/Thermodynamics/Free energy" ] ], "openalex": "W7214806288", "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0356359&type=printable", "pmcid": null, "pmid": null, "published": "2026-09-29", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/57dhbabbp28wv.ris", "sources": [ { "first_seen": "2026-10-30T12:17:37Z", "native_id": "10.1371/journal.pone.0356359", "source": "plos", "url": "https://doi.org/10.1371/journal.pone.0356359" } ], "subjects": [ { "field": "biology", "origin": "plos:cell biology", "subfield": "cell-biology" }, { "field": "biology", "origin": "plos:immunology", "subfield": "immunology" }, { "field": "medicine", "origin": "plos:cancers and neoplasms", "subfield": "oncology" } ], "title": "FABP5 regulates an immunosuppressive microenvironment in hepatocellular carcinoma through the NF-κB/PD-L1 axis", "title_text": "FABP5 regulates an immunosuppressive microenvironment in hepatocellular carcinoma through the NF-κB/PD-L1 axis", "type": "peer-reviewed", "updated_at": "2026-10-30T12:17:37Z", "url": "https://research.draconitic.com/paper/57dhbabbp28wv", "venue": "PLOS One", "versions": [] }