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While deubiquitinases have emerged as promising therapeutic targets in various cancers, a suitable target deubiquitinase for the treatment of gastric cancer has not yet been identified. Using bioinformatics analyses, we identified that upregulation of ubiquitin-specific peptidase 26 (USP26) was associated with poor patient survival in patients with gastric cancer; moreover, depletion of endogenous USP26 with short hairpin RNAs significantly suppressed the aerobic glycolysis and proliferation in tumor cells. In mechanism, USP26 was revealed to interact with and stabilize c-Myc, which is a key driver of tumor metabolism and carcinogenesis, via suppressing its polyubiquitination and degradation. In summary, these findings suggest that USP26 plays a novel oncogenic role of USP26 by forming a USP26\u2013c-Myc regulatory axis, and that targeting USP26 may be a potential therapeutic strategy for gastric cancer.<\/jats:p>","DOI":"10.1177\/10445498251389596","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T01:25:41Z","timestamp":1761182741000},"page":"662-670","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["USP26 Promotes Cell Proliferation of Gastric Cancer by Stabilizing c-Myc"],"prefix":"10.1177","volume":"44","author":[{"given":"Doudou","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an, China."},{"name":"Department of Cancer Precision Medicine, The MED-X Institute, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an, 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