Period2 downregulation inhibits glioma cell apoptosis by activating the MDM2-TP53 pathway
Niu Zhanfeng1,2, Wang Chengquan3, Xia Hechun1,2
1Department of Neurosurgery, The General Hospital of Ningxia Medical University, Yinchuan, 750004, China.
Abstract:
The Period2 (Per2) gene is an essential component of the mammalian circadian clock and is strongly linked to glioma occurrence and its response to radiotherapy. Here, we examined the role of Per2 in the response to X-ray-induced DNA damage in U343 glioma cells and in a mouse cancer model. Following low dose X-ray irradiation, we observed that lowering Per2 expression using RNAi reduces DNA damage and cell death in U343 cells and glioma tissue. Additionally, Per2 was associated with increased TP53 activity and was involved in the DNA damage during TP53-mediated apoptosis. These findings suggest that Per2, a core circadian gene, is not only a tumor suppressor gene but can also be regarded as an upstream regulator of TP53. It thus appears that Per2 is an important inhibitor of tumor growth that acts by increasing TP53 expression, DNA damage repair, and apoptosis.
Insights
The Period2 (Per2) gene, a core circadian gene, acts as a tumor suppressor by enhancing DNA damage repair and apoptosis. Lowering Per2 expression reduces cell death in glioma, suggesting its role in cancer progression.
Area of Science:
- Molecular Biology
- Cancer Research
- Chronobiology
Background:
- The Period2 (Per2) gene is integral to the mammalian circadian clock.
- Per2 is implicated in glioma development and response to radiotherapy.
Purpose of the Study:
- To investigate the role of Per2 in response to X-ray-induced DNA damage.
- To examine Per2's function in U343 glioma cells and a mouse cancer model.
Main Methods:
- RNA interference (RNAi) to reduce Per2 expression.
- X-ray irradiation of U343 glioma cells and a mouse cancer model.
- Assessment of DNA damage, cell death, and TP53 activity.
Main Results:
- Reduced Per2 expression decreased DNA damage and cell death post-irradiation.
- Per2 was linked to increased TP53 activity and TP53-mediated apoptosis.
- Per2 appears to be an upstream regulator of TP53.
Conclusions:
- Per2 functions as a tumor suppressor gene.
- Per2 inhibits tumor growth by promoting TP53 expression, DNA damage repair, and apoptosis.
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