Abstract
Growing evidence shows that deregulation of the circadian clock plays an important role in the development of malignant tumors, including gliomas. However, the molecular mechanisms of gene chnages controlling circadian rhythm in glioma cells have not been explored. Using real time polymerase chain reaction and immunohistochemistry techniques, we examined the expression of two important clock genes, cry1 and cry2, in 69 gliomas. In this study, out of 69 gliomas, 38 were cry1-positive, and 51 were cry2-positive. The expression levels of cry1 and cry2 in glioma cells were significantly different from the surrounding non-glioma cells (P<0.01). The difference in the expression rate of cry1 and cry 2 in high-grade (grade III and IV) and low-grade (grade 1 and II) gliomas was non-significant (P>0.05) but there was a difference in the intensity of immunoactivity for cry 2 between high-grade gliomas and low-grade gliomas (r=-0.384, P=0.021). In this study, we found that the expression of cry1 and cry2 in glioma cells was much lower than in the surrounding non-glioma cells. Therefore, we suggest that disturbances in cry1 and cry2 expression may result in the disruption of the control of normal circadian rhythm, thus benefiting the survival of glioma cells. Differential expression of circadian clock genes in glioma and non-glioma cells may provide a molecular basis for the chemotherapy of gliomas.
Highlights
Almost all physiological characteristics of animals and plants differ significantly between day and night
The circadian clock and cell cycle are two global regulatory systems in most eukaryotic organisms. It has been known for some time that disruption of the circadian rhythm by genetic or environmental factors causes a variety of disorders in humans, such as sleep disturbances, circadian clock in the cancer cells of most glioma cases
In nearby non-tumor brain tissue around highgrade and low-grade, the expression of cry1 are 100% and cry 2 are 100%, suggesting that several asynchronized circadian clocks may be in operation in the same glioma tissue
Summary
Almost all physiological characteristics of animals and plants differ significantly between day and night. Central and peripheral clocks generate self-sustained circadian rhythms of about 24 hours, which coordinate physiologic processes with the rhythmically changing environment (Czeisler et al, 1999; Reppert et al, 2001; Morse et al, 2002; Reppert et al, 2002). Circadian rhythms regulate diverse physiological processes, including hormone secretion, metabolism, cell proliferation and apoptosis (Young et al, 2001; Lowrey et al, 2004; Lee et al, 2005). The daily light-dark cycle synchronizes the master circadian pacemaker, located in the suprachiasmatic nuclei (SCN) of the brain, which in turn synchronizes the organism’s central clock, as well as the peripheral clocks in each cell (Reddy et al, 2005). The molecular mechanisms of circadian oscillation in the SCN and peripheral cells are based on a negative transcriptional-translational feedback loop generated by the core clock genes
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