{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T02:50:01Z","timestamp":1784688601802,"version":"3.55.0"},"reference-count":45,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>F\u2010Box Protein 32 (FBXO32), a F\u2010box protein family member, exhibits oncogenic and tumor\u2010suppressive roles in various carcinomas. However, its function and underlying molecular mechanisms in hepatocellular carcinoma (HCC) are still unknown. We observed that FBXO32 was overexpressed in HCC tissues than normal tissues, which is pertaining to poor prognosis in HCC patients. Functional tests demonstrated that FBXO32 enhanced HCC cell proliferation, invasion, and metastasis, which was confirmed in vivo using mouse models. Proteomics\u2010based approaches and computational analyses reported a positive correlation between FBXO32 and PI3K\u2013AKT pathway, identifying pleckstrin homology domain leucine\u2010rich repeat protein phosphatase 2 (PHLPP2) as an interacting protein. Mechanistically, DNA promoter hypomethylation elevated FBXO32 expression in HCC cells, promoting K48\u2010linked PHLPP2 polyubiquitination at the K592 and K942 sites through direct interactions. Notably, targeting FBXO32 significantly inhibited tumor growth in both an orthotopic HCC model and an organoid model derived from HCC patients. To sum up, this work emphasizes the part of FBXO32 in propelling HCC progression via facilitating PI3K\u2013AKT pathway activation via PHLPP2 degradation.<\/jats:p>","DOI":"10.1002\/mco2.70410","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T06:55:17Z","timestamp":1758696917000},"source":"Crossref","is-referenced-by-count":1,"title":["Hypomethylation\u2010Enhanced F\u2010Box Protein 32 Promotes Hepatocellular Carcinogenesis via Ubiquitin\u2010Mediated PHLPP2 Degradation"],"prefix":"10.1002","volume":"6","author":[{"given":"Shu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Pancreatic Spleen Surgery The Affiliated Hospital of Jiangsu University  Zhenjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Yu","sequence":"additional","affiliation":[{"name":"Hepatobiliary Center, The First Affiliated Hospital With Nanjing Medical University; Key Laboratory of Liver 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