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p53 regulates nuclear GSK-3 levels through miR-34-mediated Axin2 suppression in colorectal cancer cells

DC FieldValueLanguage
dc.contributor.author김남희-
dc.contributor.author김현실-
dc.contributor.author나정민-
dc.contributor.author유주경-
dc.contributor.author육종인-
dc.contributor.author윤호근-
dc.contributor.author차소영-
dc.contributor.author차용훈-
dc.date.accessioned2014-12-18T08:47:46Z-
dc.date.available2014-12-18T08:47:46Z-
dc.date.issued2013-
dc.identifier.issn1538-4101-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/86967-
dc.description.abstractp53 is a bona fide tumor suppressor gene whose loss of function marks the most common genetic alteration in human malignancy. Although the causal link between loss of p53 function and tumorigenesis has been clearly demonstrated, the mechanistic links by which loss of p53 potentiates oncogenic signaling are not fully understood. Recent evidence indicates that the microRNA-34 (miR-34) family, a transcriptional target of the p53, directly suppresses a set of canonical Wnt genes and Snail, resulting in p53-mediated suppression of Wnt signaling and the EMT process. In this study, we report that p53 regulates GSK-3β nuclear localization via miR-34-mediated suppression of Axin2 in colorectal cancer. Exogenous miR-34a decreases Axin2 UTR-reporter activity through multiple binding sites within the 5′ and 3′ UTR of Axin2. Suppression of Axin2 by p53 or miR-34 increases nuclear GSK-3β abundance and leads to decreased Snail expression in colorectal cancer cells. Conversely, expression of the non-coding UTR of Axin2 causes depletion of endogenous miR-34 via the miR-sponge effect together with increased Axin2 function, supporting that the RNA-RNA interactions with Axin2 transcripts act as an endogenous decoy for miR-34. Further, RNA transcripts of miR-34 target were correlated with Axin2 in clinical data set of colorectal cancer patients. Although the biological relevance of nuclear GSK-3 level has not been fully studied, our results demonstrate that the tumor suppressor p53/miR-34 axis plays a role in regulating nuclear GSK-3 levels and Wnt signaling through the non-coding UTR of Axin2 in colorectal cancer.-
dc.description.statementOfResponsibilityopen-
dc.relation.isPartOfCELL CYCLE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESH3' Untranslated Regions-
dc.subject.MESH5' Untranslated Regions-
dc.subject.MESHAntibiotics, Antineoplastic/pharmacology-
dc.subject.MESHAxin Protein/antagonists & inhibitors-
dc.subject.MESHAxin Protein/genetics-
dc.subject.MESHAxin Protein/metabolism*-
dc.subject.MESHBinding Sites-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHColorectal Neoplasms/metabolism-
dc.subject.MESHColorectal Neoplasms/pathology-
dc.subject.MESHDoxorubicin/pharmacology-
dc.subject.MESHGene Expression Regulation, Neoplastic/drug effects-
dc.subject.MESHGlycogen Synthase Kinase 3/metabolism*-
dc.subject.MESHHCT116 Cells-
dc.subject.MESHHumans-
dc.subject.MESHMicroRNAs/metabolism*-
dc.subject.MESHRNA Interference-
dc.subject.MESHRNA, Messenger/metabolism-
dc.subject.MESHRNA, Small Interfering/metabolism-
dc.subject.MESHSnail Family Transcription Factors-
dc.subject.MESHTranscription Factors/metabolism-
dc.subject.MESHTranscription, Genetic-
dc.subject.MESHTumor Suppressor Protein p53/metabolism*-
dc.subject.MESHWnt Signaling Pathway-
dc.titlep53 regulates nuclear GSK-3 levels through miR-34-mediated Axin2 suppression in colorectal cancer cells-
dc.typeArticle-
dc.contributor.collegeCollege of Dentistry (치과대학)-
dc.contributor.departmentDept. of Oral Pathology (구강병리학)-
dc.contributor.googleauthorNam Hee Kim-
dc.contributor.googleauthorYong Hoon Cha-
dc.contributor.googleauthorShi Eun Kang-
dc.contributor.googleauthorYoonmi Lee-
dc.contributor.googleauthorInhan Lee-
dc.contributor.googleauthorSo Young Cha-
dc.contributor.googleauthorJoo Kyung Ryu-
dc.contributor.googleauthorJung Min Na-
dc.contributor.googleauthorChangbum Park-
dc.contributor.googleauthorHo-Geun Yoon-
dc.contributor.googleauthorGyeong-Ju Park-
dc.contributor.googleauthorJong In Yook-
dc.contributor.googleauthorHyun Sil Kim-
dc.identifier.doi10.4161/cc.24739-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00360-
dc.contributor.localIdA01121-
dc.contributor.localIdA01234-
dc.contributor.localIdA02536-
dc.contributor.localIdA02625-
dc.contributor.localIdA03997-
dc.contributor.localIdA04000-
dc.relation.journalcodeJ00481-
dc.identifier.eissn1551-4005-
dc.identifier.pmid23624843-
dc.subject.keywordAxin2-
dc.subject.keywordGSK-3-
dc.subject.keywordSnail-
dc.subject.keywordepithelial-mesenchymal transition (EMT)-
dc.subject.keywordmiR-34)-
dc.subject.keywordmicroRNA-34 (miRNA-34-
dc.subject.keywordp53-
dc.contributor.alternativeNameKim, Nam Hee-
dc.contributor.alternativeNameKim, Hyun Sil-
dc.contributor.alternativeNameNa, Jung Min-
dc.contributor.alternativeNameRyu, Joo Kyung-
dc.contributor.alternativeNameYook, Jong In-
dc.contributor.alternativeNameYoon, Ho Geun-
dc.contributor.alternativeNameCha, So Young-
dc.contributor.alternativeNameCha, Yong Hoon-
dc.contributor.affiliatedAuthorKim, Nam Hee-
dc.contributor.affiliatedAuthorKim, Hyun Sil-
dc.contributor.affiliatedAuthorNa, Jung Min-
dc.contributor.affiliatedAuthorYook, Jong In-
dc.contributor.affiliatedAuthorYoon, Ho Geun-
dc.contributor.affiliatedAuthorCha, So Young-
dc.contributor.affiliatedAuthorCha, Yong Hoon-
dc.rights.accessRightsfree-
dc.citation.volume12-
dc.citation.number10-
dc.citation.startPage1578-
dc.citation.endPage1587-
dc.identifier.bibliographicCitationCELL CYCLE, Vol.12(10) : 1578-1587, 2013-
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers

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