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PARP3 interacts with FoxM1 to confer glioblastoma cell radioresistance

Jun-Jie Quan1, Jin-Ning Song2, Jian-Qiang Qu1

  • 1Department of Neurosurgery, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shanxi, 710004, People's Republic of China.

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
|June 5, 2015
PubMed

Insights

Poly(ADP-ribose) polymerase 3 (PARP3) is elevated in glioblastoma and drives tumor growth. Inhibiting PARP3 may enhance radiotherapy effectiveness, offering a new therapeutic strategy for glioblastoma patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Poly(ADP-ribose) polymerase 3 (PARP3) is crucial for DNA double-strand break repair and genome stability.
  • The specific role of PARP3 in glioblastoma development and its response to therapy is not well understood.

Purpose of the Study:

  • To investigate the role of PARP3 in glioblastoma tumorigenesis.
  • To evaluate PARP3 as a potential therapeutic target for glioblastoma, particularly in combination with radiotherapy.

Main Methods:

  • Analysis of PARP3 mRNA and protein levels in glioblastoma tissues.
  • In vitro knockdown of PARP3 using lentivirus-based shRNA in glioblastoma cell lines.
  • In vivo studies using a xenograft mouse model to assess tumor growth inhibition.
  • Evaluation of the radiosensitizing effect of PARP3 inhibition in combination with radiotherapy.

Main Results:

  • PARP3 expression was significantly upregulated in primary glioblastoma tissues.
  • PARP3 knockdown reduced glioblastoma cell proliferation and inhibited tumor growth in vivo.
  • Silencing PARP3 expression synergistically enhanced the radiosensitivity of glioblastoma cells.
  • PARP3 was found to interact with FoxM1, boosting its transcriptional activity and contributing to radioresistance.

Conclusions:

  • PARP3 plays a significant role in glioblastoma proliferation and radioresistance.
  • Targeting PARP3 presents a promising therapeutic strategy to overcome radioresistance in glioblastoma.
Keywords:
ApoptosisGlioblastomaPARP3Radioresistance

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