{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T08:41:53Z","timestamp":1792658513330,"version":"4.5.0"},"reference-count":29,"publisher":"Bioscientifica","issue":"10","funder":[{"DOI":"10.13039\/100017962","name":"Jiangsu Commission of Health","doi-asserted-by":"publisher","award":["No. ZDXK202222"],"award-info":[{"award-number":["No. ZDXK202222"]}],"id":[{"id":"10.13039\/100017962","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007166","name":"Jiangsu Provincial Department of Education","doi-asserted-by":"publisher","award":["26CXJH3509"],"award-info":[{"award-number":["26CXJH3509"]}],"id":[{"id":"10.13039\/501100007166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Papillary thyroid carcinoma (PTC), the most common endocrine malignancy, frequently exhibits invasive behaviors, including tumor invasion and cervical lymph node metastasis, which serve as major determinants of prognosis. However, reliable predictive biomarkers for these aggressive features remain elusive. This study systematically elucidates the tumor-suppressive role of MIB E3 ubiquitin protein ligase 2 (MIB2) in PTC and delineates its underlying molecular mechanism. Integrated bioinformatics analysis and validation in clinical specimens demonstrated significant downregulation of MIB2 in PTC tissues relative to normal thyroid counterparts, with reduced MIB2 expression strongly inversely correlated with aggressive clinicopathological parameters, including lymph node metastasis and extrathyroidal extension. Functional assays revealed that ectopic MIB2 expression markedly attenuated PTC cell proliferation, migration, and invasion in vitro and tumorigenicity in vivo, whereas MIB2 knockdown exacerbated these malignant phenotypes. Mechanistically, MIB2 directly interacted with hexokinase 2 (HK2) via its RING domain, thereby promoting K48-linked polyubiquitination and subsequent proteasomal degradation of HK2. This led to substantial suppression of HK2 protein levels, impairment of glycolytic flux, and consequent restriction of PTC cell aggressiveness. To our knowledge, this is the first demonstration that MIB2 functions as a key negative regulator of PTC invasiveness by targeting HK2 for K48-linked ubiquitination-dependent degradation, thereby modulating glycolytic metabolism. These findings establish MIB2 as a critical suppressor in PTC progression and highlight its potential as a diagnostic biomarker and therapeutic target for aggressive PTC, providing a foundation for the development of precision intervention strategies.<\/jats:p>","DOI":"10.1530\/erc-26-0049","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:18:09Z","timestamp":1791451089000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":0,"title":["MIB2-mediated ubiquitination of HK2 inhibits glycolysis in PTC"],"prefix":"10.1530","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0617-3939","authenticated-orcid":true,"given":"Lijun","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University 1 , , ,","place":["Nanjing, Jiangsu, 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