Poly(ADP-ribose) polymerase 3 (PARP3), a critical player in cellular response to DNA double-strand breaks (DSBs), plays an essential role in the maintenance of genome integrity. However, the role of PARP3 in tumorigenesis especially in glioblastoma remains largely unknown. In the present study, we found that the mRNA and protein levels of PARP3 were upregulated in primary glioblastoma tissues. Knockdown of PARP3 expression by lentivirus-based shRNA decreased cell glioblastoma proliferation and inhibited tumor growth in vivo by using a xenograft mouse model. Furthermore, we found that silencing the expression of PARP3 resulted in a synergistic radiosensitizing effect when combined with radiotherapy in glioblastoma cell lines. At the molecular level, we found that PARP3 interacted with FoxM1 to enhance its transcriptional activity and conferred glioblastoma cell radioresistance. Thus, our data suggest that PARP3 could be a therapeutic target to overcome radioresistance in glioblastoma.
PARP3 Radioresistance Glioblastoma Apoptosis
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Erpolat OP et al. Outcome of newly diagnosed glioblastoma patients treated by radiotherapy plus concomitant and adjuvant temozolomide: a long-term analysis. Tumori. 2009;95(2):191–7.PubMedGoogle Scholar
Langelier MF, Riccio AA, Pascal JM. PARP-2 and PARP-3 are selectively activated by 5′ phosphorylated DNA breaks through an allosteric regulatory mechanism shared with PARP-1. Nucleic Acids Res. 2014;42(12):7762–75.CrossRefPubMedPubMedCentralGoogle Scholar
Wang Z, et al. Glioblastoma multiforme formation and EMT: role of FoxM1 transcription factor. Curr Pharm Des. 2014;21(10):1268–71.Google Scholar
Zhang N et al. FoxM1 inhibition sensitizes resistant glioblastoma cells to temozolomide by downregulating the expression of DNA-repair gene Rad51. Clin Cancer Res. 2012;18(21):5961–71.CrossRefPubMedPubMedCentralGoogle Scholar
Zhang Y et al. FoxM1B transcriptionally regulates vascular endothelial growth factor expression and promotes the angiogenesis and growth of glioma cells. Cancer Res. 2008;68(21):8733–42.CrossRefPubMedPubMedCentralGoogle Scholar
Dai B et al. Aberrant FoxM1B expression increases matrix metalloproteinase-2 transcription and enhances the invasion of glioma cells. Oncogene. 2007;26(42):6212–9.CrossRefPubMedGoogle Scholar
Liu M et al. FoxM1B is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells. Cancer Res. 2006;66(7):3593–602.CrossRefPubMedGoogle Scholar