Circadian expression of clock- and tumor suppressor genes in human oral mucosa

Cell Physiol Biochem. 2010;26(2):155-66. doi: 10.1159/000320547. Epub 2010 Aug 24.

Abstract

Purpose: Circadian rhythms are daily oscillations of multiple biological processes driven by endogenous clocks. Imbalance of these rhythms has been associated with cancerogenesis in humans. To further elucidate the role circadian clocks have in cellular growth control, tumor suppression and cancer treatment, it is revealing to know how clock genes and clock-controlled genes are regulated in healthy humans.

Materials and methods: Therefore comparative microarray analyses were conducted investigating the relative mRNA expression of clock genes throughout a 24-hour period in cell samples obtained from oral mucosa of eight healthy diurnally active male study participants. Differentially expressed selected genes of interest were additionally evaluated using qRT-PCR.

Results: Microarray analysis revealed 33 significant differentially regulated clock genes and clock- controlled genes, throughout a one day period (6.00h, 12.00h, 18.00h, 24.00h). Hereof were 16 clock genes and 17 clock- controlled genes including tumor suppressor- and oncogenes. qRT-PCR of selected genes of interest, such as hPER2, hCRY1, hBMAL1, hCCRN4L and hSMAD5 revealed significant circadian regulations.

Conclusion: Our study revealed a proper circadian regulation profile of several clock- and tumor suppressor genes at defined points in time in the participants studied. These findings could provide important information regarding genes displaying the same expression profile in the gastrointestinal tract amounting to a physiological expression profile of healthy humans. In the future asynchronous regulations of those genes might be an additional assistant method to detect derivations distinguishing normal from malignant tissue or assessing risk factors for cancer.

MeSH terms

  • ARNTL Transcription Factors / genetics
  • ARNTL Transcription Factors / metabolism
  • CLOCK Proteins / metabolism*
  • Circadian Rhythm / genetics*
  • Cryptochromes / genetics
  • Cryptochromes / metabolism
  • Humans
  • Male
  • Middle Aged
  • Mouth Mucosa / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Period Circadian Proteins / genetics
  • Period Circadian Proteins / metabolism
  • RNA, Messenger / metabolism
  • Smad5 Protein / genetics
  • Smad5 Protein / metabolism
  • Time Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tumor Suppressor Proteins / metabolism*

Substances

  • ARNTL Transcription Factors
  • CRY1 protein, human
  • Cryptochromes
  • Nuclear Proteins
  • PER2 protein, human
  • Period Circadian Proteins
  • RNA, Messenger
  • Smad5 Protein
  • Transcription Factors
  • Tumor Suppressor Proteins
  • nocturnin
  • CLOCK Proteins