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c-Fos is a major component of activator protein (AP)-1 complex, which has been implicated in cell differentiation, proliferation, angiogenesis, invasion and metastasis. In this study, we investigated the role of c-Fos gene in glioma radiosensitivity and figured out the involved molecular mechanisms. Following downregulation of c-Fos gene by lenti-virus in glioma cell lines, we analyzed the radiosensitivity, DNA damage repair capacity, and cell cycle distribution of c-Fos. At last, we explored its prognostic value in 41 malignant glioma patients by immunohistochemistry. Our results showed that c-Fos inhibition could sensitize glioma cells to radiation by increasing radiation induced DNA double strand breaks(DSBs), disturbing the DNA damage repair process, promoting G2 cell cycle arrest and apoptosis. c-Fos protein overexpression correlated with poor prognosis in glioma patients who received standard treatment. Our findings provide new insights into the mechanism of radioresistance in malignant glioma. Therefore, c-Fos may hopefully become a novel therapeutic target for malignant glioma patients. |
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Keywords:Malignant Glioma, Radioresistance, c-Fos, prognosis |
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