期刊
MOLECULAR CANCER
卷 13, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1476-4598-13-258
关键词
OTUB1; Colorectal cancer; Metastasis; EMT; Prognostic factor
资金
- National High Technology Research and Development Program of China (863 Program) [2012AA02A204]
- National Natural Science Foundation of China [81472256, 81472252, 81272638]
- National Basic Research Program of China (973 Program) [2010CB912201, 2011CB504805]
- National Major Scientific and Technological Special Project [2012ZX09401015]
- Health & Medical Collaborative Innovation Project of Guangzhou City, China [201400000001]
- Guangdong Innovative Research Team Program [2009010058]
- Guangdong Provincial Science and Technology Projects [2011A080502010]
Background: OTUB1 (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. Methods: Two 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. Results: OTUB1 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. Conclusions: OTUB1 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.
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