{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:00:45Z","timestamp":1790715645916,"version":"4.1.0"},"reference-count":33,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 82305181, No. 82405252. No. 82474601 and No. 82305398"],"award-info":[{"award-number":["No. 82305181, No. 82405252. No. 82474601 and No. 82305398"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shenzhen Basic Research Special Natural Science Foundation Plan Project","award":["No.JCYJ20250604150049018"],"award-info":[{"award-number":["No.JCYJ20250604150049018"]}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["No. 2025A1515011830 and No. 2022A1515110099"],"award-info":[{"award-number":["No. 2025A1515011830 and No. 2022A1515110099"]}]},{"name":"Scientific Research Project of Traditional Chinese Medicine Bureau of Guangdong Province","award":["No. 20251426"],"award-info":[{"award-number":["No. 20251426"]}],"id":[{"id":"https:\/\/ror.org\/05vkkzf98","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Special Project for Clinical and Basic Sci&Tech Innovation of Guangdong Medical University, Shenzhen Key Laboratory","award":["No. ZDSYS20210623092000002"],"award-info":[{"award-number":["No. ZDSYS20210623092000002"]}]},{"name":"General Program of Traditional Chinese Medicine Research of Guangdong Province","award":["No. 20231131"],"award-info":[{"award-number":["No. 20231131"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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\u2013immune interplay in HCC, elucidating how FABP5 shapes the tumor immune microenvironment may uncover new therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u2013protein docking, molecular dynamics (MD) simulations and in vitro assays were conducted to explore the regulatory role of FABP5 in the NF-\u03baB\/PD-L1 axis. Drug screening, molecular docking and duplicate MD simulations were carried out to identify potential FABP5-targeting compounds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u2013mesenchymal 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-\u03baB pathway genes and molecular docking predicted stable complexes between I\u03baB\u03b1 and P65. Experimental validation confirmed that FABP5 drives PD-L1 upregulation in an NF-\u03baB\u2013dependent manner. Drug screening identified CZS-241 as the most promising FABP5-binding candidate, and duplicate MD simulations demonstrated a stable FABP5\u2013CZS-241 complex.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>FABP5 drives immunosuppression in HCC by inducing PD-L1 via the NF-\u03baB pathway. CZS-241 is identified as a promising FABP5-targeting compound with therapeutic potential for HCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0356359","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:01:46Z","timestamp":1790712106000},"page":"e0356359","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["FABP5 regulates an immunosuppressive microenvironment in hepatocellular carcinoma through the NF-\u03baB\/PD-L1 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