c-Fos over-expression promotes radioresistance and predicts poor prognosis in malignant glioma.
c-Fos over-expression promotes radioresistance and predicts poor prognosis in malignant glioma.
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c-Fos 过度表达可促进恶性胶质瘤的放射抗性并预测不良预后
DOI：
10.18632/oncotarget.11779
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发表时间：
2016-10-04
期刊：
影响因子：
--
通讯作者：
Li XN
中科院分区：
文献类型：
--
作者：
Liu ZG;Jiang G;Tang J;Wang H;Feng G;Chen F;Tu Z;Liu G;Zhao Y;Peng MJ;He ZW;Chen XY;Lindsay H;Xia YF;Li XN
C-Fos是激活蛋白(AP)-1复合体的主要组成部分。它与细胞分化、增殖、血管生成、侵袭和转移密切相关。为了探讨c-Fos在胶质瘤放射敏感性中的作用及其分子机制，我们通过慢病毒介导的shRNA下调了胶质瘤细胞系中c-Fos基因的表达，并分析了c-Fos基因的辐射敏感性、DNA损伤修复能力和细胞周期分布。最后，通过免疫组织化学方法探讨其在41例恶性脑胶质瘤患者中的预后价值。我们的结果表明，沉默c-Fos通过增加辐射诱导的DNA双链断裂(DSB)，干扰DNA损伤修复过程，促进G2/M细胞周期停滞，促进细胞凋亡，从而使胶质瘤细胞对辐射敏感。在接受标准治疗的恶性胶质瘤患者中，c-Fos蛋白的过度表达与预后不良相关。我们的发现为恶性胶质瘤的辐射抵抗机制提供了新的见解，并确认c-Fos是恶性胶质瘤患者潜在的新的治疗靶点。
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.