title: Properties and Clinical Relevance of Speckle-Type POZ Protein in Human Colorectal Cancer.
abstract: BACKGROUND
  The aims of this study are to evaluate the effect of Speckle-type POZ protein (SPOP) in colorectal cancer (CRC) patients and explore its significance in the prognosis.
  
  
  METHODS
  We used immunohistochemistry to detect the expression of SPOP in CRC. Moreover, this result was further confirmed at the protein and messenger RNA (mRNA) level in paired CRC specimens and matched adjacent noncancerous colon tissues by Western blotting and real-time quantitative PCR (qRT-PCR), respectively. Furthermore, we evaluate the effects of SPOP on CRC cell proliferation and migration in vitro. The Kaplan-Meier method and log-rank test were employed to compare the overall survival between SPOP low expression group and SPOP high expression group. Correlation of survival with clinicopathologic parameters, including SPOP level, was investigated with multivariate analyses.
  
  
  RESULTS
  We confirmed frequent SPOP downregulation in both mRNA (P = 0.0286) and protein (P = 0.004) levels in CRC tissues as compared to matched adjacent nontumorous tissues. Besides, the downregulated SPOP expression in CRC tissues was significantly correlated to poor differentiation (P = 0.013), distant metastasis (P = 0.003), gross type (P < 0.001), and high TNM stage (P = 0.002). Kaplan-Meier survival analysis showed that low SPOP expression exhibited a significant correlation with poor prognosis for CRC patients. Overexpression of SPOP in CRC cell lines significantly suppressed cell proliferation, migration, and clone formation. In contrast, SPOP knockdown dramatically promoted cell proliferation, migration, and clone formation in vitro. In addition, overexpression of SPOP increased E-cadherin and suppressed vimentin in HCT116 cells and silencing of SPOP reversed all these biomarkers. Furthermore, SPOP significantly downregulated MMP2 and MMP7 protein levels in HCT116 cell lines.
  
  
  CONCLUSIONS
  Our results suggest that SPOP plays a pivotal role in colorectal cancer (CRC) through mesenchymal-epithelial transition and MMPs, and it may be a potential therapeutic target in colorectal cancer.
authors.affiliation: Department of General Surgery, Affiliated Hospital of Nantong University, No. 20, Xisi Road, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Junfei
authors.initials: J
authors.lastname: Xu
authors.forename: Feiran
authors.initials: F
authors.lastname: Wang
authors.forename: Haiyan
authors.initials: H
authors.lastname: Jiang
authors.forename: Yasu
authors.initials: Y
authors.lastname: Jiang
authors.forename: Jinpeng
authors.initials: J
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
mesh_terms: D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D053208:Kaplan-Meier Estimate; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D015820:Cadherins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C509761:SPOP protein, human; D014746:Vimentin; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2