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

Abstract

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.

• Authors: Yi Zhou, Jiangxue Wu, Xiang Fu, Wuying Du, Ling Zhou, Xiangqi Meng, Hongyan Yu, Jiaxin Lin, Wen Ye, Jiani Liu, Hui Peng, Ran-Yi Liu, Changchuan Pan, Wenlin Huang
• Journal: Molecular cancer (Mol Cancer) Vol. 13 Pg. 258 (Nov 28 2014) ISSN: 1476-4598 [Electronic] England
• PMID: 25431208 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Deubiquitinating Enzymes
• OTUB1 protein, human
• Cysteine Endopeptidases

Topics

• Animals
• Biomarkers, Tumor (genetics)
• Cell Line
• Cell Line, Tumor
• Cell Movement (genetics)
• Colorectal Neoplasms (diagnosis, genetics, pathology)
• Cysteine Endopeptidases (genetics)
• Deubiquitinating Enzymes
• Down-Regulation (genetics)
• Epithelial-Mesenchymal Transition (genetics)
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• HCT116 Cells
• HEK293 Cells
• HT29 Cells
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Metastasis (genetics)
• Prognosis