Open Accessc-Fos over-expression promotes radioresistance and predicts poor prognosis in malignant glioma
Author(s) -
Zhi Gang Liu,
Guanmin Jiang,
Jiao Tang,
Hui Wang,
GuoKai Feng,
FuRong Chen,
Ziwei Tu,
Guiyun Liu,
Yu Zhao,
Ming Peng,
Zheng Wen He,
Xiao Yan Chen,
Holly Lindsay,
Yun Xia,
Xiao Nan Li
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.11779
Subject(s) - glioma , radioresistance , cell cycle , cancer research , radiosensitivity , dna damage , dna repair , apoptosis , cell cycle checkpoint , small hairpin rna , biology , medicine , radiation therapy , gene , dna , gene knockdown , genetics
c-Fos is a major component of activator protein (AP)-1 complex. It has been implicated in cell differentiation, proliferation, angiogenesis, invasion, and metastasis. To investigate the role of c-Fos in glioma radiosensitivity and to understand the underlying molecular mechanisms, we downregulated c-Fos gene expression by lentivirus-mediated shRNA in glioma cell lines and subsequently analyzed the radiosensitivity, DNA damage repair capacity, and cell cycle distribution. Finally, we explored its prognostic value in 41 malignant glioma patients by immunohistochemistry. Our results showed that silencing c-Fos sensitized glioma cells to radiation by increasing radiation-induced DNA double strand breaks (DSBs), disturbing the DNA damage repair process, promoting G2/M cell cycle arrest, and enhancing apoptosis. c-Fos protein overexpression correlated with poor prognosis in malignant glioma patients treated with standard therapy. Our findings provide new insights into the mechanism of radioresistance in malignant glioma and identify c-Fos as a potentially novel therapeutic target for malignant glioma patients.