p53/E2F7 axis promotes temozolomide chemoresistance in glioblastoma multiforme
Jiao Meng,
Wei Qian,
Zhenkun Yang,
Lingli Gong,
Daxing Xu,
Hongbo Huang,
Xinyi Jiang,
Zhening Pu,
Ying Yin,
Jian Zou
Affiliations
Jiao Meng
Department of Laboratory Medicine, Wuxi People’s Hospital, Wuxi Medical Center, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Nanjing Medical University
Wei Qian
Department of Laboratory Medicine, Wuxi People’s Hospital, Wuxi Medical Center, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Nanjing Medical University
Zhenkun Yang
Department of Laboratory Medicine, Wuxi People’s Hospital, Wuxi Medical Center, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Nanjing Medical University
Lingli Gong
Department of Laboratory Medicine, Wuxi People’s Hospital, Wuxi Medical Center, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Nanjing Medical University
Daxing Xu
Department of Laboratory Medicine, Wuxi People’s Hospital, Wuxi Medical Center, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Nanjing Medical University
Hongbo Huang
NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine
Xinyi Jiang
Department of Laboratory Medicine, Wuxi People’s Hospital, Wuxi Medical Center, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Nanjing Medical University
Zhening Pu
Department of Laboratory Medicine, Wuxi People’s Hospital, Wuxi Medical Center, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Nanjing Medical University
Ying Yin
Department of Laboratory Medicine, Wuxi People’s Hospital, Wuxi Medical Center, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Nanjing Medical University
Jian Zou
Department of Laboratory Medicine, Wuxi People’s Hospital, Wuxi Medical Center, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Nanjing Medical University
Abstract Background Glioblastoma multiforme (GBM) is the most aggressive form of brain cancer, and chemoresistance poses a significant challenge to the survival and prognosis of GBM. Although numerous regulatory mechanisms that contribute to chemoresistance have been identified, many questions remain unanswered. This study aims to identify the mechanism of temozolomide (TMZ) resistance in GBM. Methods Bioinformatics and antibody-based protein detection were used to examine the expression of E2F7 in gliomas and its correlation with prognosis. Additionally, IC50, cell viability, colony formation, apoptosis, doxorubicin (Dox) uptake, and intracranial transplantation were used to confirm the role of E2F7 in TMZ resistance, using our established TMZ-resistance (TMZ-R) model. Western blot and ChIP experiments provided confirmation of p53-driven regulation of E2F7. Results Elevated levels of E2F7 were detected in GBM tissue and were correlated with a poor prognosis for patients. E2F7 was found to be upregulated in TMZ-R tumors, and its high levels were linked to increased chemotherapy resistance by limiting drug uptake and decreasing DNA damage. The expression of E2F7 was also found to be regulated by the activation of p53. Conclusions The high expression of E2F7, regulated by activated p53, confers chemoresistance to GBM cells by inhibiting drug uptake and DNA damage. These findings highlight the significant connection between sustained p53 activation and GBM chemoresistance, offering the potential for new strategies to overcome this resistance.
