{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T04:31:52Z","timestamp":1786422712948,"version":"build-2736575974"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014718","name":"Innovative Research Group Project of the National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014718","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>RPLP0, a ribosomal protein critical for protein biosynthesis, has emerged as a multifaceted oncoprotein through its regulation of programmed cell death (PCD) pathways. Despite its established roles in tumorigenesis, its pan-cancer relevance and ferroptosis regulatory function remains unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Bioinformatics analyses utilized TCGA, GTEx, GEPIA, UALCAN, HPA, cBioPortal, TISIDB, FerrDb, BioGRID, HitPredict, and R Studio. Experimental validation in hepatocellular carcinoma (HCC) included RT-qPCR, IHC, CCK8, transwell, and colony formation assays. Ferroptosis was assessed via lipid ROS, ferrous iron, and GSH detection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our comprehensive pan-cancer analysis revealed conserved RPLP0 upregulation across malignancies, positively associated with adverse clinical outcomes. Genomic profiling identified recurrent RPLP0 alterations, while tumor microenvironment analyses demonstrated significant negative correlations between RPLP0 expression and immune cell infiltration. Focusing on hepatocellular carcinoma (HCC), experimental validation confirmed that RPLP0 depletion suppressed tumor progression via ferroptosis induction through metabolic and oxidative cascades, and RPLP0 was positively correlated with key ferroptosis suppressor GPX4.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This work advances the understanding of ribosomal protein biology by establishing RPLP0 as a pan-cancer biomarker bridging ribosome function with immune evasion, unveiling its canonical role in HCC progression, and discovering RPLP0-GPX4-mediated ferroptosis resistance axis, providing a novel therapeutic paradigm for aggressive cancers.<\/jats:p>\n                  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