Research Papers:
Period2 downregulation inhibits glioma cell apoptosis by activating the MDM2-TP53 pathway
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Abstract
Niu Zhanfeng1,2,*, Wang Chengquan3,*, Xia Hechun1,2, Wang Jun4,2, Zhang Lijian4,2, Ma Dede4,2, Liu Wenbin4,2, Yin Lei5,2
1Department of Neurosurgery, The General Hospital of Ningxia Medical University, Yinchuan, 750004, China
2Incubation Base of National Key Laboratory for Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, 750004, China
3The People’s Hospital of Liaocheng City, Liaocheng, 252000, China
4 Ningxia Medical University, Yinchuan, 750004, China
5Department of ICU, The General Hospital of Ningxia Medical University, Yinchuan, 750004, China
*These authors contributed equally to this work
Correspondence to:
Xia Hechun, e-mail: [email protected]
Keywords: period2, glioma, TP53, X-ray, U343 cells
Received: November 04, 2015 Accepted: March 16, 2016 Published: March 28, 2016
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.
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