The Circadian Gene Clock Plays an Important Role in Cell Apoptosis and the DNA Damage Response In Vitro

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Abstract

The Clock gene, an indispensable component of the circadian clock, not only modulates circadian oscillations but also regulates organismal function. We examined whether silencing the expression of the human Clock gene in glioma cells influences cell growth and induces apoptosis after irradiation. Silencing the expression of Clock in a human glioma cell line (U87MG), but not in a control glioma cell line, resulted in increased apoptosis and cell cycle arrest. Moreover, silencing Clock expression altered the expression of apoptosis-related genes. The protein levels of c-Myc and Cyclin B1 were downregulated, but those of p53 were upregulated, in human Clock-silenced U87MG cells compared with control cells. Our results suggest that the circadian gene human Clock may play an important role in carcinogenesis by inhibiting apoptotic cell death via attenuating proapoptotic signaling.

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