{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:38:49Z","timestamp":1792525129832,"version":"4.5.0"},"reference-count":22,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    RNA\u2010binding protein RBM4 regulates post\u2010transcriptional programs, but its role in shaping the hepatocellular carcinoma (HCC) tumor immune microenvironment (TIME) is unclear. We hypothesized that RBM4 enhances S100A10 mRNA stability to drive immune evasion. RBM4\u2013S100A10 coupling was interrogated by expression profiling, RIP\u2010qPCR, actinomycin D chase, and 3\u2032UTR reporter assays. Gain\/loss models (OE\u2010RBM4, shS100A10) were used to assess migration\/invasion and apoptosis. Immune consequences were evaluated by CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell co\u2010culture (ELISA for Granzyme B, IFN\u2010\u03b3, TNF\u2010\u03b1; IL\u201010, TGF\u2010\u03b2) and immunofluorescence. Western blots probed cPLA2\/5\u2010LOX signaling. Subcutaneous\/orthotopic models measured tumor growth, CD8\n                    <jats:sup>+<\/jats:sup>\n                    infiltration, and effector subsets; S100A10 silencing and PD\u20101 blockade served as interventions. RBM4 positively correlated with S100A10 and bound the S100A10 3\u2032UTR, increasing mRNA stability and 3\u2032UTR\u2010dependent reporter activity. RBM4 overexpression promoted migration\/invasion and reduced apoptosis, whereas S100A10 knockdown reversed these phenotypes. In the TIME context, RBM4 reduced CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell effector function (lower Granzyme B\/IFN\u2010\u03b3\/TNF\u2010\u03b1) while elevating IL\u201010\/TGF\u2010\u03b2, accompanied by diminished CD8\n                    <jats:sup>+<\/jats:sup>\n                    infiltration and fewer CD8\n                    <jats:sup>+<\/jats:sup>\n                    GZMB\n                    <jats:sup>+<\/jats:sup>\n                    \/CD8\n                    <jats:sup>+<\/jats:sup>\n                    TNF\u2010\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    cells in vivo. Mechanistically, RBM4 activated the cPLA2\/5\u2010LOX axis (increased phospho\u2010forms with stable totals). S100A10 silencing or PD\u20101 blockade mitigated immune suppression and restrained tumor growth, indicating pathway specificity and therapeutic tractability. RBM4 enhances S100A10 mRNA stability, remodels the HCC TIME, suppresses CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell effector function, and promotes immune evasion; targeting the RBM4\u2013S100A10 axis may improve responses to PD\u20101 immunotherapy.\n                  <\/jats:p>","DOI":"10.1002\/mc.70197","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:46:32Z","timestamp":1792521992000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RBM4 Stabilizes S100A10 mRNA to Remodel the Tumor Immune Microenvironment and Promote Immune Evasion in Hepatocellular Carcinoma"],"prefix":"10.1002","author":[{"given":"YiWen","family":"Zhang","sequence":"first","affiliation":[{"name":"Yangzhou University Yangzhou City Jiangsu Province China"},{"name":"Department of Oncology Nantong Haimen People's Hospital Nantong City Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LanLan","family":"Gui","sequence":"additional","affiliation":[{"name":"Department of Oncology Nantong Haimen People's Hospital Nantong City Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YanRong","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Oncology Nantong Haimen People's Hospital Nantong City Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LiLi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Oncology Nantong Haimen People's Hospital Nantong City Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JuanJuan","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Oncology Nantong Haimen People's Hospital Nantong City Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ManQin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Oncology Nantong Haimen People's Hospital Nantong City Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6338-2317","authenticated-orcid":false,"given":"JunXing","family":"Huang","sequence":"additional","affiliation":[{"name":"Yangzhou University Yangzhou City Jiangsu Province China"},{"name":"Department of Oncology Taizhou People's Hospital Affiliated to Yangzhou University Taizhou City Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,20]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-024-01294-6"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-025-00986-3"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40164-024-00539-x"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-024-09483-8"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.01.040"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.03.011"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S125250"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-024-01931-z"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-68528-y"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2022-327998"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-023-01487-5"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02128-8"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.107729"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.31083\/j.fbl2902089"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep28222"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.23499"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-023-11127-3"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1325-x"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2035"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.36203"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2018.9751"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1548234"}],"container-title":["Molecular 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