title: Cryptochrome 1 overexpression correlates with tumor progression and poor prognosis in patients with colorectal cancer.
abstract: BACKGROUND
  Clock genes drive about 5-15% of genome-wide mRNA expression, and disruption of the circadian clock may deregulate the cell's normal biological functions. Cryptochrome 1 is a key regulator of the circadian feedback loop and plays an important role in organisms. The present study was conducted to investigate the expression of Cry1 and its prognostic significance in colorectal cancer (CRC). In addition, the function of Cry1 in human CRC was investigated in cell culture models.
  
  
  METHODS
  Real-time quantitative PCR, Western blot analysis and immunohistochemistry were used to explore Cry1 expression in CRC cell lines and primary CRC clinical specimens. MTT and colony formation assays were used to determine effects on cellular proliferation ability. The animal model was used to explore the Cry1 impact on the tumor cellular proliferation ability in vivo. Transwell assays were performed to detect the migration ability of the cell lines. Statistical analyzes were applied to evaluate the diagnostic value and the associations of Cry1 expression with clinical parameters.
  
  
  RESULTS
  Cry1 expression was up regulated in the majority of the CRC cell lines and 168 primary CRC clinical specimens at the protein level. Clinical pathological analysis showed that Cry1 expression was significantly correlated with lymph node metastasis (p = 0.004) and the TNM stage (p = 0.003). High Cry1 expression was associated with poor overall survival in CRC patients (p = 0.010). Experimentally, we found that up-regulation of Cry1 promoted the proliferation and migration of HCT116 cells, while down-regulation of Cry1 inhibited the colony formation and migration of SW480 cells.
  
  
  CONCLUSIONS
  These results suggest that Cry1 likely plays important roles in CRC development and progression andCry1 may be a prognostic biomarker and a promising therapeutic target for CRC.
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Yu
authors.forename: Xiangqi
authors.initials: X
authors.lastname: Meng
authors.forename: Jiangxue
authors.initials: J
authors.lastname: Wu
authors.forename: Changchuan
authors.initials: C
authors.lastname: Pan
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Ying
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Ranyi
authors.initials: R
authors.lastname: Liu
authors.forename: Wenlin
authors.initials: W
authors.lastname: Huang
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D056931:Cryptochromes / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D011379:Prognosis; D016019:Survival Analysis
chemical_list: C538963:CRY1 protein, human; D056931:Cryptochromes; D009363:Neoplasm Proteins