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The regulatory mechanisms in tumors are complex and diverse, encompassing a range of cellular processes such as proliferation, apoptosis, inflammation, autophagy, and drug resistance. However, the functional role of USP14 in gastric cancer remains unclear. In the current investigation, a significant upregulation of USP14 expression was observed in gastric cancer, and its overexpression was associated with an unfavorable prognosis among patients. The involvement of USP14 is indispensable for promoting the growth, motility, and infiltration of gastric cancer cells, as revealed by our findings. Further investigations revealed that USP14 interacts with KPNA2 and is responsible for deubiquitinating it by removing ubiquitin. Moreover, the deubiquitylation process mediated by USP14 was found to be critically dependent on the K48 residue of ubiquitin. The knockdown of USP14 significantly suppressed the proliferation, migration, and invasion of gastric cancer cells. This effect was attributed to the regulation of c-MYC nuclear translocation through KPNA2 deubiquitination. The findings underscore the imperative for further evaluation of the potential therapeutic significance of USP14 in gastric cancer.<\/jats:p>","DOI":"10.1038\/s41419-025-08065-2","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:00:56Z","timestamp":1761051656000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The deubiquitination enzyme USP14 promotes the tumourigenesis of gastric cancer by enhancing c-MYC nuclear translocation through deubiquitination of KPNA2"],"prefix":"10.1038","volume":"16","author":[{"given":"Jia","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houyi","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbo","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5606-5450","authenticated-orcid":false,"given":"Erhu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"8065_CR1","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1093\/annonc\/mdw040","volume":"27","author":"NY Chia","year":"2016","unstructured":"Chia NY, Tan P. 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(Henan, China), and the studies were approved by the Medical Ethics Committee of Tongxu County People\u2019s Hospital of Henan Province. All of the patients were informed consent. Animal welfare and experimental procedures were carried out in accordance with the Guide for the Care and Use of Laboratory Animals and approved by the animal ethics committee of Southwest University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"737"}}