640 990

Cited 96 times in

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

 Nam Hee Kim  ;  Yong Hoon Cha  ;  Shi Eun Kang  ;  Yoonmi Lee  ;  Inhan Lee  ;  So Young Cha  ;  Joo Kyung Ryu  ;  Jung Min Na  ;  Changbum Park  ;  Ho-Geun Yoon  ;  Gyeong-Ju Park  ;  Jong In Yook  ;  Hyun Sil Kim 
 CELL CYCLE, Vol.12(10) : 1578-1587, 2013 
Journal Title
Issue Date
3' Untranslated Regions ; 5' Untranslated Regions ; Antibiotics, Antineoplastic/pharmacology ; Axin Protein/antagonists & inhibitors ; Axin Protein/genetics ; Axin Protein/metabolism* ; Binding Sites ; Cell Line, Tumor ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; Doxorubicin/pharmacology ; Gene Expression Regulation, Neoplastic/drug effects ; Glycogen Synthase Kinase 3/metabolism* ; HCT116 Cells ; Humans ; MicroRNAs/metabolism* ; RNA Interference ; RNA, Messenger/metabolism ; RNA, Small Interfering/metabolism ; Snail Family Transcription Factors ; Transcription Factors/metabolism ; Transcription, Genetic ; Tumor Suppressor Protein p53/metabolism* ; Wnt Signaling Pathway
Axin2 ; GSK-3 ; Snail ; epithelial-mesenchymal transition (EMT) ; miR-34) ; microRNA-34 (miRNA-34 ; p53
p53 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.
Files in This Item:
T201301672.pdf Download
Appears in Collections:
2. College of Dentistry (치과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral and Maxillofacial Surgery (구강악안면외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Nam Hee(김남희) ORCID logo https://orcid.org/0000-0002-3087-5276
Kim, Hyun Sil(김현실) ORCID logo https://orcid.org/0000-0003-3614-1764
Na, Jung Min(나정민)
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
Yoon, Ho Geun(윤호근) ORCID logo https://orcid.org/0000-0003-2718-3372
Cha, So Young(차소영) ORCID logo https://orcid.org/0000-0002-2810-3883
Cha, Yong Hoon(차용훈) ORCID logo https://orcid.org/0000-0003-1761-3260
사서에게 알리기


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.