Silencing NPAS2 promotes cell growth and invasion in DLD-1 cells and correlated with poor prognosis of colorectal cancer

Biochem Biophys Res Commun. 2014 Jul 25;450(2):1058-62. doi: 10.1016/j.bbrc.2014.06.104. Epub 2014 Jun 27.

Abstract

Emerging evidences show that circadian rhythm disorder is an important factor of tumor initiation and development. Neuronal PAS domain protein2 (NPAS2), which is the largest circadian gene, has been proved to be a novel prognostic biomarker in breast cancer and non-Hodgkin's lymphoma. However, the potential functions of NPAS2 in colorectal cancer are still unknown. In our present study, we detected the mRNA expressions of NPAS2 in 108 CRC patients by RT-PCR, and found that NPAS2 expression was significantly down-regulated in tumor tissues than that in NATs. Clinicopathologic analysis revealed that low expression of NPAS2 was associated with the tumor size, TNM stage and tumor distance metastasis in colorectal cancer (p<0.05). Furthermore, we effectively down-regulated NPAS2 mRNA expression by transfecting RNA interfere fragments into DLD-1 cells, and our results in vitro demonstrated that silencing NPAS2 expression could promote cell proliferation, cell invasion and increase the wound healing ability (p<0.05). However, down-regulating NPAS2 expression did not influence the apoptotic rate in DLD-1 cells (p>0.05). In conclusion, our study suggested that NPAS2, functioned as a potential tumor suppressor gene, could serve as a promising target and potential prognostic indicator for colorectal cancer.

Keywords: Circadian gene; Colorectal cancer; NPAS2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Female
  • Gene Silencing
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness*
  • Neoplasm Metastasis
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Prognosis
  • RNA, Messenger / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • NPAS2 protein, human
  • Nerve Tissue Proteins
  • RNA, Messenger