{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T13:51:46Z","timestamp":1782481906355,"version":"3.54.5"},"reference-count":52,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"vor","delay-in-days":29,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Despite its aggressiveness and unfavorable prognosis, the key molecular drivers of Hepatocellular carcinoma (HCC) are still not fully defined. The role of ribosomal protein S8 (RPS8) in HCC development and its regulatory mechanisms received little attention. We investigated the role of RPS8 in HCC progression by delineating its biological functions, clinical relevance, and mechanistic underpinnings. We conducted comprehensive multi\u2010omics analysis using public datasets (TCGA, GEO) to evaluate RPS8 expression and its prognostic value in HCC. Single\u2010cell RNA\u2010seq was utilized to map the distribution of RPS8 expression within the tumor microenvironment. The biological functions of RPS8 were validated through a series of in\u00a0vitro assays (e.g., colony formation, Transwell, wound healing) and in\u00a0vivo subcutaneous xenograft models using RPS8 knockdown and overexpression systems. Whole\u2010transcriptome sequencing was performed to identify the downstream pathways regulated by RPS8. RPS8 was elevated in HCC at both the transcriptional and protein levels, and its overexpression independently signaled poor prognosis. In functional assays, RPS8 increased HCC cell proliferation, migration, and invasion in\u00a0vitro and stimulated tumor growth in\u00a0vivo. This pro\u2010tumorigenic activity was associated with the induction of epithelial\u2010mesenchymal transition (EMT) and angiogenesis. Mechanistically, we revealed that RPS8 exerts these effects by activating the endoplasmic reticulum (ER) stress pathway. Furthermore, high RPS8 expression was associated with a remodeled tumor immune microenvironment, characterized by increased CD8+ T cell infiltration. Findings identify RPS8 as a critical oncogene that promotes HCC progression via activation of ER stress. RPS8 can be leveraged as a prognostic biomarker and as a potential focus of therapy in HCC.<\/jats:p>","DOI":"10.1002\/biof.70116","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T07:37:35Z","timestamp":1780126655000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi\u2010Omics Analysis and Mechanistic Validation Reveal\n                    <scp>RPS8<\/scp>\n                    as a Novel Prognostic Biomarker and Therapeutic Target for Hepatocellular Carcinoma"],"prefix":"10.1002","volume":"52","author":[{"given":"Lichen","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Liver Surgery The First Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"Key Laboratory of Hepatosplenic Surgery Ministry of Education  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery The First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery The First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sile","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Organ Transplantation Zhengzhou People's Hospital  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fukai","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery The First Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"Key Laboratory of Hepatosplenic Surgery Ministry of Education  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anatomy Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2589-5560","authenticated-orcid":false,"given":"Zhaoyang","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery The First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaming","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery The First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21871"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.06.021"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010024\u201002075\u2010w"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010020\u201000240\u20103"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.08.021"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575\u2010019\u20100186\u2010y"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010015\u20100239\u20101"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.10.052"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40364\u2010021\u201000311\u2010x"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20211577"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578\u2010024\u201001316\u20103"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41417\u2010024\u201000861\u2010w"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2014.128"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2020.7634"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201017\u20100032"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2013\u20100314TR"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.06.028"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2019.04.010"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70365"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31428"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420\u2010023\u201001355\u20108"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2022.09.012"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21218177"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.70151"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.3055"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.763"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26188801"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935\u2010025\u201003803\u20100"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15748"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2131"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072\u2010024\u201010696\u20100"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935\u2010025\u201003954\u20100"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202500930R"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI16886"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010pathol\u2010012513\u2010104649"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3701"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.50.33741"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010020\u20102327\u20101"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.asjsur.2022.06.057"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.730847"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0168\u20108278(03)00029\u20101"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2025.5543"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114897"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010020\u201001702\u2010y"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010025\u201007356\u2010y"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1133308"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.12.004"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32740"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abg3750"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201012370\u20108"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935\u2010023\u201003097\u20100"}],"container-title":["BioFactors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biof.70116","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/biof.70116","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biof.70116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T13:32:08Z","timestamp":1782480728000},"score":1,"resource":{"primary":{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/10.1002\/biof.70116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":52,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/biof.70116"],"URL":"https:\/\/doi.org\/10.1002\/biof.70116","archive":["Portico"],"relation":{},"ISSN":["0951-6433","1872-8081"],"issn-type":[{"value":"0951-6433","type":"print"},{"value":"1872-8081","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2026-01-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70116"}}