Circadian Expression of Clock- and Tumor Suppressor Genes in Human Oral Mucosa

Aug 28, 2010Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology

Daily patterns of body clock and tumor-preventing genes in human mouth lining

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Abstract

Microarray analysis identified 33 significant differentially regulated clock genes and clock-controlled genes throughout a 24-hour period.

Sixteen clock genes and seventeen clock-controlled genes, including tumor suppressor and oncogenes, were significantly regulated.
Circadian regulation was confirmed for selected genes such as hPER2, hCRY1, hBMAL1, hCCRN4L, and hSMAD5 using qRT-PCR.
The study indicates a proper circadian regulation profile of specific genes at defined time points in healthy individuals.
Findings may inform on gene expression profiles in the gastrointestinal tract, relevant for distinguishing normal from malignant tissues.

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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.

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Circadian Expression of Clock- and Tumor Suppressor Genes in Human Oral Mucosa

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