title: Potential role of TRIM3 as a novel tumour suppressor in colorectal cancer (CRC) development.
abstract: OBJECTIVE
  Colorectal cancer (CRC) is the third leading cause of cancer-related mortality in the United States. Recent cancer genome-sequencing efforts and complementary functional studies have led to the identification of a collection of candidate 'driver' genes involved in CRC tumorigenesis. Tripartite motif (TRIM3) is recently identified as a tumour suppressor in glioblastoma but this tumour-suppressive function has not been investigated in CRC.
  
  
  METHODS
  In this study, we investigated the potential role of TRIM3 as a tumour suppressor in CRC development by manipulating the expression of TRIM3 in two authentic CRC cell lines, HCT116 and DLD1, followed by various functional assays, including cell proliferation, colony formation, scratch wound healing, soft agar, and invasion assays. Xenograft experiment was performed to examine in vivo tumour-suppressive properties of TRIM3.
  
  
  RESULTS
  Small-interfering RNA (siRNA) mediated knockdown of TRIM3 conferred growth advantage in CRC cells. In contrast, overexpression of TRIM3 affected cell survival, cell migration, anchorage independent growth and invasive potential in CRC cells. In addition, TRIM3 was found to be down-regulated in human colon cancer tissues compared with matched normal colon tissues. Overexpression of TRIM3 significantly inhibited tumour growth in vivo using xenograft mouse models. Mechanistic investigation revealed that TRIM3 can regulate p53 protein level through its stabilisation.
  
  
  CONCLUSIONS
  TRIM3 functions as a tumour suppressor in CRC progression. This tumour-suppressive function is exerted partially through regulation of p53 protein. Therefore, this protein may represent a novel therapeutic target for prevention or intervention of CRC.
authors.affiliation: a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Heping District , Tianjin , China ;
authors.forename: Mei-Yu
authors.initials: MY
authors.lastname: Piao
authors.affiliation: a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Heping District , Tianjin , China ;
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Cao
authors.affiliation: a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Heping District , Tianjin , China ;
authors.forename: Na-Na
authors.initials: NN
authors.lastname: He
authors.affiliation: a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Heping District , Tianjin , China ;
authors.forename: Meng-Que
authors.initials: MQ
authors.lastname: Xu
authors.affiliation: a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Heping District , Tianjin , China ;
authors.forename: Wen-Xiao
authors.initials: WX
authors.lastname: Dong
authors.affiliation: a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Heping District , Tianjin , China ;
authors.forename: Wei-Qiang
authors.initials: WQ
authors.lastname: Wang
authors.affiliation: a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Heping District , Tianjin , China ;
authors.forename: Bang-Mao
authors.initials: BM
authors.lastname: Wang
authors.affiliation: b Department of Gastroenterology , Tanggu Traditional Chinese Medicine Hospital of Tianjin Binhai New Area , Tanggu Binhai New Area , Tianjin , China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental; D012333:RNA, Messenger / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D002352:Carrier Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C426543:TRIM3 protein, human
keywords: Colorectal cancer; TRIM3; p53; tumour suppressor