{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:14:01Z","timestamp":1788185641035,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Lung cancer remains the leading cause of cancer\u2010associated death, and aerobic glycolysis is a key hallmark of cancer. Ubiquitination is a post\u2010translational modification involved in the regulation of lung cancer progression. The aim of this study was to investigate E3 ubiquitin ligase mouse double minute 2 (MDM2) and its ubiquitination on myosin heavy chain 11 (MYH11) in lung cancer progression and glycolytic reprogramming. Expression of MYH11 was analyzed using online databases. MDM2 and MYH11 mRNA and protein detection was performed by qPCR and Western blot. Cell proliferation, migration, and invasion were respectively detected using colony formation assay, wound healing assay, and transwell assay. Glycolysis was evaluated by measuring lactate production and glucose consumption. Epithelial\u2010mesenchymal transition (EMT) and glycolysis\u2010associated proteins were measured using Western blot. Xenograft tumor model was established for in vivo analysis. Co\u2010immunoprecipitation (Co\u2010IP) assay was performed to assess ubiquitination effect of MDM2 on MYH11 and their protein interaction. MYH11 was a down\u2010regulated gene in lung cancer and it negatively correlated with glycolysis. Lung cancer cell proliferation, migration, invasion, EMT, and glycolysis were significantly inhibited following MYH11 overexpression. Tumor growth in vivo was also reduced by MYH11. Mechanistically, MDM2 mediated ubiquitination of MYH11 to induce MYH11 protein degradation and downregulation. Knockdown of MDM2 suppressed the malignant phenotypes of lung cancer cells via enhancing MYH11 protein stability in vitro and in vivo. These results suggest that MDM2 reduces MYH11 expression via ubiquitination\u2010mediated degradation of MYH11 protein, thereby enhancing lung cancer cell proliferation, migration\/invasion, EMT and glycolysis, and ultimately promoting tumor progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mc.70172","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T13:17:31Z","timestamp":1788182251000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["E3 Ubiquitin Ligase MDM2 Contributes to Proliferation, Migration\/Invasion, Epithelial\u2010Mesenchymal Transition, and Glycolytic Reprogramming in Lung Cancer via Ubiquitinating and Degrading MYH11 Protein"],"prefix":"10.1002","author":[{"given":"Yanfeng","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Tangdu Hospital Fourth Military Medical University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenting","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Tangdu Hospital Fourth Military Medical University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Tangdu Hospital Fourth Military Medical University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Tangdu Hospital Fourth Military Medical University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongtong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Tangdu Hospital Fourth Military Medical University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6500-0376","authenticated-orcid":false,"given":"Zheng","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Tangdu Hospital Fourth Military Medical University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.3390\/ijms26052049","article-title":"Lung Cancer\u2010Epidemiology, Pathogenesis, Treatment and Molecular Aspect (Review of Literature)","volume":"26","author":"Smolarz B.","year":"2025","journal-title":"International Journal of Molecular Sciences"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1038\/s41571-023-00798-3","article-title":"The Global Burden of Lung Cancer: Current Status and Future Trends","volume":"20","author":"Leiter 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