Oncotarget

Research Papers:

Aberrant rhythmic expression of cryptochrome2 regulates the radiosensitivity of rat gliomas

Wang Fan, Li Caiyan, Zhu Ling _ and Zhao Jiayun

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Oncotarget. 2017; 8:77809-77818. https://doi.org/10.18632/oncotarget.20835

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Abstract

Wang Fan1,*, Li Caiyan2,*, Zhu Ling1 and Zhao Jiayun1

1Department of Neurosurgery, The First People’s Hospital of Jingmen, Jingmen 448000, China

2The Center of Cancer Prevention, The Second People’s Hospital of Jingmen, Jingmen 448000, China

*These authors have contributed equally to this work

Correspondence to:

Zhu Ling, email: [email protected]

Zhao Jiayun, email: [email protected]

Keywords: circadian rhythm, cry2, glioma, radiotherapeutic sensitivity

Received: February 17, 2017    Accepted: August 17, 2017    Published: September 12, 2017

ABSTRACT

In this study, we investigated the role of the clock regulatory protein cryptochrome 2 (Cry2) in determining the radiosensitivity of C6 glioma cells in a rat model. We observed that Cry2 mRNA and protein levels showed aberrant rhythmic periodicity of 8 h in glioma tissues, compared to 24 h in normal brain tissue. Cry2 mRNA and protein levels did not respond to irradiation in normal tissues, but both were increased at the ZT4 (low Cry2) and ZT8 (high Cry2) time points in gliomas. Immunohistochemical staining of PCNA and TUNEL assays demonstrated that high Cry2 expression in glioma tissues was associated with increased cell proliferation and decreased apoptosis. Western blot analysis showed that glioma cell fate was independent of p53, but was probably dependent on p73, which was more highly expressed at ZT4 (low Cry2) than at ZT8 (high Cry2). Levels of both p53 and p73 were unaffected by irradiation in normal brain tissues. These findings suggest aberrant rhythmic expression of Cry2 influence on radiosensitivity in rat gliomas.


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