OTUB1 promotes metastasis and serves as a marker of poor prognosis in colorectal cancer

Molecular Cancer

Research

Hui Peng¹  Changchuan Pan²  Wuying Du³  Yi Zhou³  Xiangqi Meng³  Jiani Liu³  Ran-yi Liu³  Jiangxue Wu³  Ling Zhou³  Hongyan Yu³  Wen Ye³  Xiang Fu³  Jiaxin Lin³  Wenlin Huang⁴ 

[1] Department of Colorectal and Anal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China;Medical Oncology, Sichuan Cancer Hospital and Institute, Second People’s Hospital of Sichuan Province, 614000, Chengdu, PR China;State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center;Collaborative Innovation Center for Cancer Medicine, No. 651 Dongfeng East Road, 510060, Guangzhou, China;State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center;Collaborative Innovation Center for Cancer Medicine, No. 651 Dongfeng East Road, 510060, Guangzhou, China;CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, PR China;Guangdong Provincial Key Laboratory of Tumor-targeted Drug and Guangzhou Enterprise Key Laboratory of Gene Medicine, Guangzhou Doublle Bioproducts Inc, Guangzhou, Guangdong, China;

关键词: OTUB1;    Colorectal cancer;    Metastasis;    EMT;    Prognostic factor;   

DOI  :  10.1186/1476-4598-13-258

 received in 2014-03-27, accepted in 2014-11-03,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundOTUB1 (OTU deubiquitinase, ubiquitin aldehyde binding 1) is a deubiquitinating enzyme (DUB) that belongs to the OTU (ovarian tumor) superfamily. The aim of this study was to clarify the role of OTUB1 in colorectal cancer (CRC) and to identify the mechanism underlying its function.MethodsTwo hundred and sixty CRC samples were subjected to association analysis of OTUB1 expression and clinicopathological variables using immunohistochemical (IHC) staining. Overexpression of OTUB1 was achieved in SW480 and DLD-1 cells, and downregulation of OTUB1 was employed in SW620 cells. Then, migration and invasion assays were performed, and markers of the epithelial-mesenchymal transition (EMT) were analyzed. In addition, hepatic metastasis models in mice were used to validate the function of OTUB1 in vivo.ResultsOTUB1 was overexpressed in CRC tissues, and the expression level of OTUB1 was associated with metastasis. A high expression level of OTUB1 was also associated with poor survival, and OTUB1 served as an independent prognostic factor in multivariate analysis. OTUB1 also promoted the metastasis of CRC cell lines in vitro and in vivo by regulating EMT.ConclusionsOTUB1 promotes CRC metastasis by facilitating EMT and acts as a potential distant metastasis marker and prognostic factor in CRC. Targeting OTUB1 may be helpful for the treatment of CRC.

【 授权许可】

Unknown   
© Zhou et al.; licensee BioMed Central. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.