c-Fos over-expression promotes radioresistance and predicts poor prognosis in malignant glioma.
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.
Key Laboratory of Translational Radiation Oncology, Hunan Province, Department of Radiotherapy, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 421001, P.R. China.
Zhi-Gang
ZG
Liu
Department of Clinical Laboratory, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 421001, P.R. China.
Guanmin
G
Jiang
Key Laboratory of Translational Radiation Oncology, Hunan Province, Department of Radiotherapy, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 421001, P.R. China.
Jiao
J
Tang
Key Laboratory of Translational Radiation Oncology, Hunan Province, Department of Radiotherapy, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 421001, P.R. China.
Hui
H
Wang
State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P.R. China.
Guokai
G
Feng
State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P.R. China.
Furong
F
Chen
State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P.R. China.
Ziwei
Z
Tu
Key Laboratory of Translational Radiation Oncology, Hunan Province, Department of Radiotherapy, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 421001, P.R. China.
Guiyun
G
Liu
Key Laboratory of Translational Radiation Oncology, Hunan Province, Department of Radiotherapy, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 421001, P.R. China.
Yu
Y
Zhao
Translational Medicine Center, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 421001, P.R. China.
Ming-Jing
MJ
Peng
Department of Neurosurgery, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 421001, P.R. China.
Zheng-Wen
ZW
He
Department of Pathology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 421001, P.R. China.
Xiao-Yan
XY
Chen
Laboratory of Molecular Neuro-Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston TX, 77030, USA.
Holly
H
Lindsay
State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P.R. China.
Yun-Fei
YF
Xia
Laboratory of Molecular Neuro-Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston TX, 77030, USA.
Xiao-Nan
XN
Li
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000528:radiation effects; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy; D002453:Cell Cycle / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D011836:Radiation Tolerance; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D055815:Young Adult
D014408:Biomarkers, Tumor; D016760:Proto-Oncogene Proteins c-fos
c-Fos; malignant glioma; prognosis; radioresistance