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Ribosomal proteins have recently emerged as critical regulators of tumorigenesis beyond their classical roles in protein synthesis. Here, we investigated the expression, functional significance, and underlying mechanism of RPL27 in gastric cancer. RPL27 was markedly upregulated in gastric cancer tissues compared with adjacent normal tissues, as demonstrated by Western blotting and immunohistochemistry. High RPL27 expression was significantly associated with poor overall survival, suggesting its potential as a prognostic biomarker. Functional assays revealed that RPL27 knockdown substantially suppressed gastric cancer cell proliferation, migration, and invasion. Transcriptomic analysis identified FMC1 as a key downstream molecule of RPL27, mediating its regulatory effects on mitochondrial function, including alterations in membrane potential, morphology, DNA copy number, and ATP5A expression. Rescue experiments demonstrated that either FMC1 knockdown or treatment with the OXPHOS inhibitor oligomycin A partially reversed the malignant phenotypes induced by RPL27 overexpression. Furthermore, RPL27 knockdown significantly inhibited tumor growth in a xenograft mouse model. Collectively, these findings establish RPL27 as a novel oncogenic driver in gastric cancer and demonstrate that it promotes tumor progression through FMC1\u2010dependent regulation of oxidative phosphorylation. The RPL27\u2010FMC1\u2010mitochondrial function axis may thus represent a promising vulnerability for therapeutic intervention in gastric cancer.<\/jats:p>","DOI":"10.1002\/cbin.70178","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T16:39:28Z","timestamp":1781541568000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RPL27 Promotes Gastric Cancer Progression by Enhancing Oxidative Phosphorylation Via FMC1"],"prefix":"10.1002","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1365-9107","authenticated-orcid":false,"given":"Yan","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of General Surgery The First Affiliated Hospital of Anhui Medical University Hefei China"},{"name":"Department of General Surgery Anhui Public Health Clinical Center Hefei 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