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 important role in other biological processes, including pathways involved in the proliferation and apoptosis of tumor cells. In this study, we investigated the mechanism by which the downregulated expression of PER1 promotes the apoptosis of wild-type P53 human glioma U343 cells exposed to X-rays. Methods:U343 cells were exposed to 6 mV 10 Gy X-ray irradiation after infection with an shRNA lentivirus to reduce the expression of PER1 and were analyzed by SCGE analysis, flow cytometry, qRT-PCR, and western blotting. Result: SCGE analysis revealed that compared with the controls, U343 cells expressing low levels of PER1 showed minor DNA damage when exposed to X-ray irradiation (P < 0.05), and the flow cytometry assay showed lower death rates (P < 0.05). RT-PCR and western blot analysis both revealed decreased expression of CHK2 and P53, which regulate DNA damage and repair via the CHK2-P53 pathway, and decreased expression of C-MYC, which is related to cell apoptosis. Conclusion:Our research suggests that PER1 may play an important role in tumor radiotherapy, which is attributable to enhanced chk2-P53 signaling and proapoptotic processes. These findings provide a new target for the clinical treatment of glioma and a reliable basis for postradiation therapy and gene therapy for glioma and other cancers.