C-Fos over-expression promotes radioresistance and predicts poor prognosis in malignant glioma

Zhi Gang Liu*, Guanmin Jiang, Jiao Tang, Hui Wang, Guokai Feng, Furong Chen, Ziwei Tu, Guiyun Liu, Yu Zhao, Ming Jing Peng, Zheng Wen He, Xiao Yan Chen, Holly Lindsay, Yun Fei Xia, Xiao Nan Li

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)65946-65956
Number of pages11
JournalOncotarget
Volume7
Issue number40
DOIs
StatePublished - 2016

Keywords

  • C-Fos
  • Malignant glioma
  • Prognosis
  • Radioresistance

ASJC Scopus subject areas

  • Oncology

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