The Circadian Gene Per1 Plays an Important Role in Radiation-Induced Apoptosis and DNA Damage in Glioma

Abstract

Objective: Period1 (PER1), a core circadian gene, not only modulates circadian rhythm but may also play an<br />important role in other biological processes, including pathways involved in the proliferation and apoptosis of tumor<br />cells. In this study, we investigated the mechanism by which the downregulated expression of PER1 promotes the<br />apoptosis of wild-type P53 human glioma U343 cells exposed to X-rays. Methods:U343 cells were exposed to 6 mV<br />10 Gy X-ray irradiation after infection with an shRNA lentivirus to reduce the expression of PER1 and were analyzed<br />by SCGE analysis, flow cytometry, qRT-PCR, and western blotting. Result: SCGE analysis revealed that compared with<br />the controls, U343 cells expressing low levels of PER1 showed minor DNA damage when exposed to X-ray irradiation<br />(P<0.05), and the flow cytometry assay showed lower death rates (P<0.05). RT-PCR and western blot analysis both<br />revealed decreased expression of CHK2 and P53, which regulate DNA damage and repair via the CHK2-P53 pathway,<br />and decreased expression of C-MYC, which is related to cell apoptosis. Conclusion:Our research suggests that PER1<br />may play an important role in tumor radiotherapy, which is attributable to enhanced chk2-P53 signaling and proapoptotic<br />processes. These findings provide a new target for the clinical treatment of glioma and a reliable basis for postradiation<br />therapy and gene therapy for glioma and other cancers.