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


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.


CONCLUSIONS
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.
Zieker
Derek
D
Department of General, Visceral and Transplant Surgery, University of Tuebingen, Tuebingen, Germany. derek.zieker@med.uni-tuebingen.de
Jenne
Isabel
I
Koenigsrainer
Ingmar
I
Zdichavsky
Marty
M
Nieselt
Kay
K
Buck
Katharina
K
Zieker
Judith
J
Beckert
Stefan
S
Glatzle
Joerg
J
Spanagel
Rainer
R
Koenigsrainer
Alfred
A
Northoff
Hinnak
H
Loeffler
Markus
M
D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism; D056926:CLOCK Proteins / Q000378:metabolism*; D002940:Circadian Rhythm / Q000235:genetics*; D056931:Cryptochromes / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051902:Smad5 Protein / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D056930:ARNTL Transcription Factors; C538963:CRY1 protein, human; D056931:Cryptochromes; D009687:Nuclear Proteins; C421902:PER2 protein, human; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D051902:Smad5 Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C102804:nocturnin; D056926:CLOCK Proteins