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000308667 0247_ $$2ISSN$$a1743-9159
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000308667 041__ $$aEnglish
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000308667 1001_ $$00000-0002-4575-8224$$aYan, Qian$$b0
000308667 245__ $$aLINC00476 cooperates with ARIH2 and suppresses pancreatic cancer progression by inducing VIM ubiquitination.
000308667 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2026
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000308667 520__ $$aPancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid malignancies, with the majority of cases typically diagnosed at an advanced, inoperable stage. Dysregulated long noncoding RNAs (lncRNAs) play a significant role in the progression of PDAC; however, the underlying mechanisms, especially the interactions between lncRNAs and protein modifications, remain poorly understood.We initially screened for potential markers among pancreatic cancer-associated lncRNAs using public databases. The involvement of LINC00476 in PDAC cell proliferation, migration, and invasion was confirmed through both in vivo and in vitro experiments. To dissect the molecular mechanisms underlying LINC00476-mediated regulation of PDAC progression and metastasis, we utilized RNA pull-down assays, RNA immunoprecipitation (RIP) assays, Co-immunoprecipitation (Co-IP) assays, and rescue experiments.Our findings identify LINC00476 as a novel lncRNA that is generally downregulated in PDAC tissues and correlates with more unfavorable clinicopathological features and poorer patient outcomes. Functionally, LINC00476 suppressed PDAC cell proliferation and invasion in vitro and inhibited lung metastasis in vivo. Mechanistically, LINC00476 directly bound vimentin (VIM) and recruited the E3 ubiquitin ligase Ariadne homolog 2 (ARIH2), promoting K29-linked polyubiquitination of VIM at Lys373 residue and subsequent proteasomal degradation. In a patient-derived xenograft (PDX) model, overexpression of ARIH2 led to a significant reduction in VIM protein levels and tumor growth (P < 0.05).Our data suggest that LINC00476 enhances VIM ubiquitination and degradation by recruiting ARIH2, highlighting the role of LINC00476 in PDAC progression and indicating that the overexpression of LINC00476 or ARIH2 may serve as a promising therapeutic strategy for PDAC.
000308667 536__ $$0G:(DE-HGF)POF4-312$$a312 - Funktionelle und strukturelle Genomforschung (POF4-312)$$cPOF4-312$$fPOF IV$$x0
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000308667 650_7 $$2Other$$aARIH2
000308667 650_7 $$2Other$$aLINC00476
000308667 650_7 $$2Other$$apancreatic ductal adenocarcinoma (PDAC)
000308667 650_7 $$2Other$$aubiquitination (Ub)
000308667 650_7 $$2Other$$avimentin (VIM)
000308667 650_7 $$2NLM Chemicals$$aRNA, Long Noncoding
000308667 650_7 $$2NLM Chemicals$$aVimentin
000308667 650_7 $$0EC 2.3.2.27$$2NLM Chemicals$$aUbiquitin-Protein Ligases
000308667 650_7 $$2NLM Chemicals$$aVIM protein, human
000308667 650_2 $$2MeSH$$aHumans
000308667 650_2 $$2MeSH$$aRNA, Long Noncoding: metabolism
000308667 650_2 $$2MeSH$$aRNA, Long Noncoding: genetics
000308667 650_2 $$2MeSH$$aPancreatic Neoplasms: pathology
000308667 650_2 $$2MeSH$$aPancreatic Neoplasms: genetics
000308667 650_2 $$2MeSH$$aPancreatic Neoplasms: metabolism
000308667 650_2 $$2MeSH$$aPancreatic Neoplasms: mortality
000308667 650_2 $$2MeSH$$aUbiquitination
000308667 650_2 $$2MeSH$$aAnimals
000308667 650_2 $$2MeSH$$aDisease Progression
000308667 650_2 $$2MeSH$$aCell Line, Tumor
000308667 650_2 $$2MeSH$$aCell Proliferation: genetics
000308667 650_2 $$2MeSH$$aVimentin: metabolism
000308667 650_2 $$2MeSH$$aCarcinoma, Pancreatic Ductal: pathology
000308667 650_2 $$2MeSH$$aCarcinoma, Pancreatic Ductal: genetics
000308667 650_2 $$2MeSH$$aCarcinoma, Pancreatic Ductal: metabolism
000308667 650_2 $$2MeSH$$aCarcinoma, Pancreatic Ductal: mortality
000308667 650_2 $$2MeSH$$aMice
000308667 650_2 $$2MeSH$$aUbiquitin-Protein Ligases: metabolism
000308667 650_2 $$2MeSH$$aUbiquitin-Protein Ligases: genetics
000308667 650_2 $$2MeSH$$aGene Expression Regulation, Neoplastic
000308667 650_2 $$2MeSH$$aMale
000308667 650_2 $$2MeSH$$aFemale
000308667 650_2 $$2MeSH$$aCell Movement: genetics
000308667 7001_ $$aChen, Yubin$$b1
000308667 7001_ $$0P:(DE-He78)e4252c07d7a2feedcb6c943766b7c84c$$aLi, Zhenchong$$b2$$eFirst author$$udkfz
000308667 7001_ $$aRuan, Shiye$$b3
000308667 7001_ $$aZhang, Zhongyan$$b4
000308667 7001_ $$aCui, Jinwei$$b5
000308667 7001_ $$aShi, Hexian$$b6
000308667 7001_ $$aFang, Jike$$b7
000308667 7001_ $$aWang, Hailiang$$b8
000308667 7001_ $$aYang, Jiayu$$b9
000308667 7001_ $$aHuang, Shanzhou$$b10
000308667 7001_ $$aZhang, Chuanzhao$$b11
000308667 7001_ $$aHou, Baohua$$b12
000308667 773__ $$0PERI:(DE-600)2201966-2$$a10.1097/JS9.0000000000003596$$gVol. 112, no. 1, p. 666 - 682$$n1$$p666 - 682$$tInternational journal of surgery$$v112$$x1743-9191$$y2026
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