Cryptochrome 1 overexpression correlates with tumor progression and poor prognosis in patients with colorectal cancer

PLoS One. 2013 Apr 23;8(4):e61679. doi: 10.1371/journal.pone.0061679. Print 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Cryptochromes / genetics*
  • Cryptochromes / metabolism
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Organ Specificity
  • Prognosis
  • Survival Analysis

Substances

  • CRY1 protein, human
  • Cryptochromes
  • Neoplasm Proteins

Grant support

This work was supported by grants from the National Basic Research Program of China (973 Program, No. 2011CB504805, No. 2010CB52994), from National Natural Science Foundation of China (30973448) and Guangdong Recruitment Program of Creative Research Group. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.